MMPs Cancer Research Results

MMPs, Matrix metalloproteinases: Click to Expand ⟱
Source:
Type:
Family of zinc-dependent proteolytic enzymes that play a key role in degrading the extracellular matrix (ECM).; are metalloproteinases that are calcium-dependent zinc-containing endopeptidases;[1] other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.[2]
MMP secretion: matrix metalloproteinase (MMP) is a kind of enzymes secreted.
by tumor cell to degrade ECM, facilitating the migration of tumor cells.

MMPs are generally considered protumorigenic due to their role in promoting tumor invasion, metastasis, and angiogenesis. They facilitate the breakdown of the extracellular matrix, allowing cancer cells to invade surrounding tissues and spread to distant sites.
Scientific Papers found: Click to Expand⟱
4549- AgNPs,    Silver nanoparticles: Synthesis, medical applications and biosafety
- Review, Var, NA - Review, Diabetic, NA
ROS↑, action mechanisms of AgNPs, which mainly involve the release of silver ions (Ag+), generation of reactive oxygen species (ROS), destruction of membrane structure.
eff↑, briefly introduce a new type of Ag particles smaller than AgNPs, silver Ångstrom (Å, 1 Å = 0.1 nm) particles (AgÅPs), which exhibit better biological activity and lower toxicity compared with AgNPs.
other↝, This method involves reducing silver ions to silver atoms 9, and the process can be divided into two steps, nucleation and growth
DNAdam↑, antimicrobial mechanisms of AgNPs includes destructing bacterial cell walls, producing reactive oxygen species (ROS) and damaging DNA structure
EPR↑, Due to the enhanced permeability and retention (EPR) effect, tumor cells preferentially absorb NPs-sized bodies than normal tissues
eff↑, Large surface area may lead to increased silver ions (Ag+) released from AgNPs, which may enhance the toxicity of nanoparticles.
eff↑, Our team prepared Ångstrom silver particles, capped with fructose as stabilizer, can be stable for a long time
TumMeta↓, AgNPs can induce tumor cell apoptosis through inactivating proteins and regulating signaling pathways, or blocking tumor cell metastasis by inhibiting angiogenesis
angioG↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
*Bacteria↓, Rather than Gram-positive bacteria, AgNPs show a stronger effect on the Gram-negative ones. This may be due to the different thickness of cell wall between two kinds of bacteria
*eff↑, In general, as particle size decreases, the antibacterial effect of AgNPs increases significantly
*AntiViral↑, AgNPs with less than 10 nm size exhibit good antiviral activity 185, 186, which may be due to their large reaction area and strong adhesion to the virus surface.
*AntiFungal↑, Some studies confirm that AgNPs exhibit good antifungal properties against Colletotrichum coccodes, Monilinia sp. 178, Candida spp.
eff↑, The greater cytotoxicity and more ROS production are observed in tumor cells exposed to high positive charged AgNPs
eff↑, Nanoparticles exposed to a protein-containing medium are covered with a layer of mixed protein called protein corona. formation of protein coronas around AgNPs can be a prerequisite for their cytotoxicity
TumCP↓, Numerous experiments in vitro and in vivo have proved that AgNPs can decrease the proliferation and viability of cancer cells.
tumCV↓,
P53↝, gNPs can promote apoptosis by up- or down-regulating expression of key genes, such as p53 242, and regulating essential signaling pathways, such as hypoxia-inducible factor (HIF) pathway
HIF-1↓, Yang et al. found that AgNPs could disrupt the HIF signaling pathway by attenuating HIF-1 protein accumulation and downstream target genes expression
TumCCA↑, Cancer cells treated with AgNPs may also show cell cycle arrest 160, 244
lipid-P↑, Ag+ released by AgNPs induces oxidation of glutathione, and increases lipid peroxidation in cellular membranes, resulting in cytoplasmic constituents leaking from damaged cells
ATP↓, mitochondrial function can be inhibited by AgNPs via disrupting mitochondrial respiratory chain, suppressing ATP production
Cyt‑c↑, and the release of Cyt c, destroy the electron transport chain, and impair mitochondrial function
MMPs↓, AgNPs can also inhibit the progression of tumors by inhibiting MMPs activity.
PI3K↓, Various studies support that AgNPs can deprive cancer cells of both nutrients and oxygen via inhibiting angiogenesis
Akt↓,
*Wound Healing↑, AgNPs exhibit good properties in promoting wound repair and bone healing, as well as inhibition of inflammation.
*Inflam↓,
*Bone Healing↑,
*glucose↓, blood glucose level of diabetic rats decreased when treated with AgNPs for 14 days and 21 days without significant acute toxicity.
*AntiDiabetic↑,
*BBB↑, The small-sized AgNPs are easy to penetrate the body and cross biological barriers like the blood-brain barrier and the blood-testis barrier

278- ALA,    The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment
- Review, NA, NA
ROS↑, direct anticancer effect of the antioxidant ALA is manifested as an increase in intracellular ROS levels in cancer cells
NRF2↑, enhance the activity of the anti-inflammatory protein nuclear factor erythroid 2–related factor 2 (Nrf2), thereby reducing tissue damage
Inflam↓,
frataxin↑,
*BioAv↓, Oral ALA has a bioavailability of approximately 30% due to issues such as poor stability in the stomach, low solubility, and hepatic degradation.
ChemoSen↑, ALA can enhance the functionality of various other anticancer drugs, including 5-fluorouracil in colon cancer cells and cisplatin in MCF-7 breast cancer cells
Hif1a↓, it is inferred that lipoic acid may inhibit the expression of HIF-1α
eff↑, act as a synergistic agent with natural polyphenolic substances such as apigenin and genistein
FAK↓, ALA inhibits FAK activation by downregulating β1-integrin expression and reduces the levels of MMP-9 and MMP-2
ITGB1↓,
MMP2↓,
MMP9↓,
EMT↓, ALA inhibits the expression of EMT markers, including Snail, vimentin, and Zeb1
Snail↓,
Vim↓,
Zeb1↓,
P53↑, ALA also stimulates the mutant p53 protein and depletes MGMT
MGMT↓, depletes MGMT by inhibiting NF-κB signalling, thereby inducing apoptosis
Mcl-1↓,
Bcl-xL↓,
Bcl-2↓,
survivin↓,
Casp3↑,
Casp9↑,
BAX↑,
p‑Akt↓, ALA inhibits the activation of tumour stem cells by reducing Akt phosphorylation.
GSK‐3β↓, phosphorylation and inactivation of GSK3β
*antiOx↑, indirect antioxidant protection through metal chelation (ALA primarily binds Cu2+ and Zn2+, while DHLA can bind Cu2+, Zn2+, Pb2+, Hg2+, and Fe3+) and the regeneration of certain endogenous antioxidants, such as vitamin E, vitamin C, and glutathione
*ROS↓, ALA can directly quench various reactive species, including ROS, reactive nitrogen species, hydroxyl radicals (HO•), hypochlorous acid (HclO), and singlet oxygen (1O2);
selectivity↑, In normal cells, ALA acts as an antioxidant by clearing ROS. However, in cancer cells, it can exert pro-oxidative effects, inducing pathways that restrict cancer progression.
angioG↓, Combining these two hypotheses, it can be hypothesized that ALA may regulate copper and HIF-2α to limit tumor angiogenesis.
MMPs↓, ALA was shown to inhibit invasion by decreasing the mRNA levels of key matrix metalloproteinases (MMPs), specifically MMP2 and MMP9, which are crucial for the metastatic process
NF-kB↓, ALA has been shown to enhance the efficacy of the chemotherapeutic drug paclitaxel in breast and lung cancer cells by inhibiting the NF-κB signalling pathway and the functions of integrin β1/β3 [138,139]
ITGB3↓,
NADPH↓, ALA has been shown to inhibit NADPH oxidase, a key enzyme closely associated with NP, including NOX4

1547- Api,    Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading
- Review, NA, NA
angioG↓,
EMT↓,
CSCs↓,
TumCCA↑,
Dose∅, Dried parsley 45,035ug/g: Dried chamomille flower 3000–5000ug/g: Parsley 2154.6ug/g:
ROS↑, activity of Apigenin has been linked to the induction of oxidative stress in cancer cells
MMP↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity
Catalase↓, catalase and glutathione (GSH), molecules involved in alleviating oxidative stress, were downregulated after Apigenin
GSH↓,
PI3K↓, suppression of the PI3K/Akt and NF-κB
Akt↓,
NF-kB↓,
OCT4↓, glycosylated form of Apigenin (i.e., Vitexin) was able to suppress stemness features of human endometrial cancer, as documented by the downregulation of Oct4 and Nanog
Nanog↓,
SIRT3↓, inhibition of sirtuin-3 (SIRT3) and sirtuin-6 (SIRT6) protein levels
SIRT6↓,
eff↑, ability of Apigenin to interfere with CSC features is often enhanced by the co-administration of other flavonoids, such as chrysin
eff↑, Apigenin combined with a chemotherapy agent, temozolomide (TMZ), was used on glioblastoma cells and showed better performance in cell arrest at the G2 phase compared with Apigenin or TMZ alone,
Cyt‑c↑, release of cytochrome c (Cyt c)
Bax:Bcl2↑, Apigenin has been shown to induce the apoptosis death pathway by increasing the Bax/Bcl-2 ratio
p‑GSK‐3β↓, Apigenin has been shown to prevent activation of phosphorylation of glycogen synthase kinase-3 beta (GSK-3β)
FOXO3↑, Apigenin administration increased the expression of forkhead box O3 (FOXO3)
p‑STAT3↓, Apigenin can induce apoptosis via inhibition of STAT3 phosphorylation
MMP2↓, downregulation of the expression of MMP-2 and MMP-9
MMP9↓,
COX2↓, downregulation of PI3K/Akt in leukemia HL60 cells [156,157] and of COX2, iNOS, and reactive oxygen species (ROS) accumulation in breast cancer cells
MMPs↓, triggering intracellular ROS accumulation and loss of mitochondrial integrity, as proved by low MMP in Apigenin-treated cells
NRF2↓, suppressed the nuclear factor erythroid 2-related factor 2 (Nrf2)
HDAC↓, inhibition of histone deacetylases (HDACs) is the mechanism through which Apigenin induces apoptosis in prostate cancer cells
Telomerase↓, Apigenin has been shown to downregulate telomerase activity
eff↑, Indeed, co-administration with 5-fluorouracil (5-FU) increased the efficacy of Apigenin in human colon cancer through p53 upregulation and ROS accumulation
eff↑, Apigenin synergistically enhances the cytotoxic effects of Sorafenib
eff↑, pretreatment of pancreatic BxPC-3 cells for 24 h with a low concentration of Apigenin and gemcitabine caused the inhibition of the GSK-3β/NF-κB signaling pathway, leading to the induction of apoptosis
eff↑, In NSCLC cells, compared to monotherapy, co-treatment with Apigenin and naringenin increased the apoptotic rate through ROS accumulation, Bax/Bcl-2 increase, caspase-3 activation, and mitochondrial dysfunction
eff↑, Several studies have shown that Apigenin-induced autophagy may play a pro-survival role in cancer therapy; in fact, inhibition of autophagy has been shown to exacerbate the toxicity of Apigenin
XIAP↓,
survivin↓,
CK2↓,
HSP90↓,
Hif1a↓,
FAK↓,
EMT↓,

1537- Api,    Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer
- Review, PC, NA
TumCP↓,
TumCCA↑,
Apoptosis↑,
MMPs↓,
Akt↓,
*BioAv↑, delivery systems (nanosuspension, polymeric micelles, liposomes).
*BioAv↓, low solubility of apigenin in water (1.35 μg/mL) and its high permeability
Half-Life∅, (appearing in blood circulation after 3.9 h)
Hif1a↓, (HIF-1α) is targeted by apigenin in several cancers such as, ovarian cancer, prostate cancer, and lung cancer
GLUT1↓, GLUT-1 is blocked by apigenin (0–100 μM) under normoxic conditions
VEGF↓,
ChemoSen↑, apigenin can be applied as a chemosensitizer
ROS↑, accumulation of ROS produced were stimulated
Bcl-2↓, down-regulation of anti-apoptotic factors Bcl-2 and Bcl-xl as well as the up-regulation of apoptotic factors Bax and Bim.
Bcl-xL↓,
BAX↑,
BIM↑,

2640- Api,    Apigenin: A Promising Molecule for Cancer Prevention
- Review, Var, NA
chemoPv↑, considerable potential for apigenin to be developed as a cancer chemopreventive agent.
ITGB4↓, apigenin inhibits hepatocyte growth factor-induced MDA-MB-231 cells invasiveness and metastasis by blocking Akt, ERK, and JNK phosphorylation and also inhibits clustering of β-4-integrin function at actin rich adhesive site
TumCI↓,
TumMeta↓,
Akt↓,
ERK↓,
p‑JNK↓,
*Inflam↓, The anti-inflammatory properties of apigenin are evident in studies that have shown suppression of LPS-induced cyclooxygenase-2 and nitric oxide synthase-2 activity and expression in mouse macrophages
*PKCδ↓, Apigenin has been reported to inhibit protein kinase C activity, mitogen activated protein kinase (MAPK), transformation of C3HI mouse embryonic fibroblasts and the downstream oncogenes in v-Ha-ras-transformed NIH3T3 cells (43, 44).
*MAPK↓,
EGFR↓, Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells
CK2↓, apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells
TumCCA↑, apigenin induces a reversible G2/M and G0/G1 arrest by inhibiting p34 (cdc2) kinase activity, accompanied by increased p53 protein stability
CDK1↓, inhibiting p34 (cdc2) kinase activity
P53↓,
P21↑, Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer
Bax:Bcl2↑, Apigenin treatment has been shown to alter the Bax/Bcl-2 ratio in favor of apoptosis, associated with release of cytochrome c and induction of Apaf-1, which leads to caspase activation and PARP-cleavage
Cyt‑c↑,
APAF1↑,
Casp↑,
cl‑PARP↑,
VEGF↓, xposure of endothelial cells to apigenin results in suppression of the expression of VEGF, an important factor in angiogenesis via degradation of HIF-1α protein
Hif1a↓,
IGF-1↓, oral administration of apigenin suppresses the levels of IGF-I in prostate tumor xenografts and increases levels of IGFBP-3, a binding protein that sequesters IGF-I in vascular circulation
IGFBP3↑,
E-cadherin↑, apigenin exposure to human prostate carcinoma DU145 cells caused increase in protein levels of E-cadherin and inhibited nuclear translocation of β-catenin and its retention to the cytoplasm
β-catenin/ZEB1↓,
HSPs↓, targets of apigenin include heat shock proteins (61), telomerase (68), fatty acid synthase (69), matrix metalloproteinases (70), and aryl hydrocarbon receptor activity (71) HER2/neu (72), casein kinase 2 alpha
Telomerase↓,
FASN↓,
MMPs↓,
HER2/EBBR2↓,
CK2↓,
eff↑, The combination of sulforaphane and apigenin resulted in a synergistic induction of UGT1A1
AntiAg↑, Apigenin inhibit platelet function through several mechanisms including blockade of TxA
eff↑, ex vivo anti-platelet effect of aspirin in the presence of apigenin, which encourages the idea of the combined use of aspirin and apigenin in patients in which aspirin fails to properly suppress the TxA
FAK↓, Apigenin inhibits expression of focal adhesion kinase (FAK), migration and invasion of human ovarian cancer A2780 cells.
ROS↑, Apigenin generates reactive oxygen species, causes loss of mitochondrial Bcl-2 expression, increases mitochondrial permeability, causes cytochrome C release, and induces cleavage of caspase 3, 7, 8, and 9 and the concomitant cleavage of the inhibitor
Bcl-2↓,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp7↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑IAP2↑,
AR↓, significant decrease in AR protein expression along with a decrease in intracellular and secreted forms of PSA. Apigenin treatment of LNCaP cells
PSA↓,
p‑pRB↓, apigenin inhibited hyperphosphorylation of the pRb protein
p‑GSK‐3β↓, Inhibition of p-Akt by apigenin resulted in decreased phosphorylation of GSK-3beta.
CDK4↓, both flavonoids exhibited cell growth inhibitory effects which were due to cell cycle arrest and downregulation of the expression of CDK4
ChemoSen↑, Combination therapy of gemcitabine and apigenin enhanced anti-tumor efficacy in pancreatic cancer cells (MiaPaca-2, AsPC-1)
Ca+2↑, apigenin in neuroblastoma SH-SY5Y cells resulted in increased apoptosis, which was associated with increases in intracellular free [Ca(2+)] and Bax:Bcl-2 ratio, mitochondrial release of cytochrome c and activation of caspase-9, calpain, caspase-3,12
cal2↑,

3160- Ash,    Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal
- Review, Var, NA
TumCCA↑, withaferin A suppressed cell proliferation in prostate, ovarian, breast, gastric, leukemic, and melanoma cancer cells and osteosarcomas by stimulating the inhibition of the cell cycle at several stages, including G0/G1 [86], G2, and M phase
H3↑, via the upregulation of phosphorylated Aurora B, H3, p21, and Wee-1, and the downregulation of A2, B1, and E2 cyclins, Cdc2 (Tyr15), phosphorylated Chk1, and Chk2 in DU-145 and PC-3 prostate cancer cells.
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycE/CCNE↓,
CDC2↓,
CHK1↓,
Chk2↓,
p38↑, nitiated cell death in the leukemia cells by increasing the expression of p38 mitogen-activated protein kinases (MAPK)
MAPK↑,
E6↓, educed the expression of human papillomavirus E6/E7 oncogenes in cervical cancer cells
E7↓,
P53↑, restored the p53 pathway causing the apoptosis of cervical cancer cells.
Akt↓, oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation,
FOXO3↑,
ROS↑, the generation of reactive oxygen species, histone H2AX phosphorylation, and mitochondrial membrane depolarization, indicating that withaferin A can cause the oxidative stress-mediated killing of oral cancer cells [
γH2AX↑,
MMP↓,
mitResp↓, withaferin A inhibited the expansion of MCF-7 and MDA-MB-231 human breast cancer cells by ROS production, owing to mitochondrial respiration inhibition
eff↑, combination treatment of withaferin A and hyperthermia induced the death of HeLa cells via a decrease in the mitochondrial transmembrane potential and the downregulation of the antiapoptotic protein myeloid-cell leukemia 1 (MCL-1)
TumCD↑,
Mcl-1↓,
ER Stress↑, . Withaferin A also attenuated the development of glioblastoma multiforme (GBM), both in vitro and in vivo, by inducing endoplasmic reticulum stress via activating the transcription factor 4-ATF3-C/EBP homologous protein (ATF4-ATF3-CHOP)
ATF4↑,
ATF3↑,
CHOP↑,
NOTCH↓, modulating the Notch-1 signaling pathway and the downregulation of Akt/NF-κB/Bcl-2 . withaferin A inhibited the Notch signaling pathway
NF-kB↓,
Bcl-2↓,
STAT3↓, Withaferin A also constitutively inhibited interleukin-6-induced phosphorylation of STAT3,
CDK1↓, lowering the levels of cyclin-dependent Cdk1, Cdc25C, and Cdc25B proteins,
β-catenin/ZEB1↓, downregulation of p-Akt expression, β-catenin, N-cadherin and epithelial to the mesenchymal transition (EMT) markers
N-cadherin↓,
EMT↓,
Cyt‑c↑, depolarization and production of ROS, which led to the release of cytochrome c into the cytosol,
eff↑, combinatorial effect of withaferin A and sulforaphane was also observed in MDA-MB-231 and MCF-7 breast cancer cells, with a dramatic reduction of the expression of the antiapoptotic protein Bcl-2 and an increase in the pro-apoptotic Bax level, thus p
CDK4↓, downregulates the levels of cyclin D1, CDK4, and pRB, and upregulates the levels of E2F mRNA and tumor suppressor p21, independently of p53
p‑RB1↓,
PARP↑, upregulation of Bax and cytochrome c, downregulation of Bcl-2, and activation of PARP, caspase-3, and caspase-9 cleavage
cl‑Casp3↑,
cl‑Casp9↑,
NRF2↑, withaferin A binding with Keap1 causes an increase in the nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels, which in turn, regulates the expression of antioxidant proteins that can protect the cells from oxidative stress.
ER-α36↓, Decreased ER-α
LDHA↓, inhibited growth, LDHA activity, and apoptotic induction
lipid-P↑, induction of oxidative stress, increased lipid peroxidation,
AP-1↓, anti-inflammatory qualities of withaferin A are specifically attributed to its inhibition of pro-inflammatory molecules, α-2 macroglobulin, NF-κB, activator protein 1 (AP-1), and cyclooxygenase-2 (COX-2) inhibition,
COX2↓,
RenoP↑, showing strong evidence of the renoprotective potential of withaferin A due to its anti-inflammatory activity
PDGFR-BB↓, attenuating the BB-(PDGF-BB) platelet growth factor
SIRT3↑, by increasing the sirtuin3 (SIRT3) expression
MMP2↓, withaferin A inhibits matrix metalloproteinase-2 (MMP-2) and MMP-9,
MMP9↓,
NADPH↑, but also provokes mRNA stimulation for a set of antioxidant genes, such as NADPH quinone dehydrogenase 1 (NQO1), glutathione-disulfide reductase (GSR), Nrf2, heme oxygenase 1 (HMOX1),
NQO1↑,
GSR↑,
HO-1↑,
*SOD2↑, cardiac ischemia-reperfusion injury model. Withaferin A triggered the upregulation of superoxide dismutase SOD2, SOD3, and peroxiredoxin 1(Prdx-1).
*Prx↑,
*Casp3?, and ameliorated cardiomyocyte caspase-3 activity
eff↑, combination with doxorubicin (DOX), is also responsible for the excessive generation of ROS
Snail↓, inhibition of EMT markers, such as Snail, Slug, β-catenin, and vimentin.
Slug↓,
Vim↓,
CSCs↓, highly effective in eliminating cancer stem cells (CSC) that expressed cell surface markers, such as CD24, CD34, CD44, CD117, and Oct4 while downregulating Notch1, Hes1, and Hey1 genes;
HEY1↓,
MMPs↓, downregulate the expression of MMPs and VEGF, as well as reduce vimentin, N-cadherin cytoskeleton proteins,
VEGF↓,
uPA↓, and protease u-PA involved in the cancer cell metastasis
*toxicity↓, A was orally administered to Wistar rats at a dose of 2000 mg/kg/day and had no adverse effects on the animals
CDK2↓, downregulated the activation of Bcl-2, CDK2, and cyclin D1
CDK4↓, Another study also demonstrated the inhibition of Hsp90 by withaferin A in a pancreatic cancer cell line through the degradation of Akt, cyclin-dependent kinase 4 Cdk4,
HSP90↓,

4812- ASTX,    Astaxanthin suppresses the metastasis of colon cancer by inhibiting the MYC-mediated downregulation of microRNA-29a-3p and microRNA-200a
- in-vitro, CRC, HCT116
miR-29b↑, AXT increases miR-29a-3p and miR-200a expression, and thereby suppresses the expression of MMP2 and ZEB1, respectively.
miR-200b↑,
MMP2↓, Astaxanthin suppresses MMP2 activity through upregulation of miR-29a-3p
Zeb1↓,
EMT↓, As a result, AXT represses the epithelial-mesenchymal transition (EMT) of CRC cells.
Apoptosis↑, AXT suppresses oral carcinomas by inducing apoptosis through the inhibition of Erk/MAPK and PI3K/Akt signaling
ERK↓,
MAPK↓,
PI3K↓,
Akt↓,
MMPs↓, AXT reduces the metastasis of cancer cells by decreasing the expression of MMPs,
TumMeta↓, Astaxanthin suppresses the metastatic activity of colon cancer cell in in vivo model

4811- ASTX,    Astaxanthin reduces MMP expressions, suppresses cancer cell migrations, and triggers apoptotic caspases of in vitro and in vivo models in melanoma
- vitro+vivo, Melanoma, A375 - vitro+vivo, Melanoma, A2058
ROS↓, Astaxanthin reduces melanoma ROS in a dose-dependent manner.
MMPs↓, Astaxanthin inhibits cellular MMPs to suppress migration and metastasis.
TumCMig↓,
TumMeta↓,
TumCCA↑, Astaxanthin induces sub-G1 arrest to trigger apoptosis in vitro and in vivo.
antiOx↑, Because astaxanthin is a potent scavenger of free radicals and quencher of reactive oxygen and nitrogen species, its antioxidant effects are even stronger than those of carotene carotenoids
MMP1↓, Astaxanthin treatment inhibited expressions of MMP-1, -2 and -9 in a dose-dependent manner.
MMP2↓,
MMP9↓,

5365- AV,    Aloe Vera Polysaccharides as Therapeutic Agents: Benefits Versus Side Effects in Biomedical Applications
- Review, Nor, NA - Review, IBD, NA - Review, Diabetic, NA
*Wound Healing↑, Traditionally recognized for its anti-inflammatory and antimicrobial effects, which are very important in wound healing, the Aloe Vera relies on its polysaccharides
*Imm↑, which confer immunomodulatory, antioxidant, and tissue-regenerative properties.
*antiOx↑,
*AntiDiabetic↑, graphical abstract
*AntiCan↑,
*Inflam↓, The anti-inflammatory properties of Aloe Vera polysaccharides are primarily mediated through the inhibition of key inflammatory pathways.
*NF-kB↓, Acemannan and other polysaccharides suppress the activation of nuclear factor-kappa B (NF-κB), a transcription factor that regulates the expression of pro-inflammatory genes.
*COX2↓, By inhibiting NF-κB [48,49], Aloe Vera polysaccharides reduce the production of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX),
*5LO↓,
*IL1β↓, Aloe Vera polysaccharides downregulate the expression of pro-inflammatory cytokines like IL-1β, IL-6, and TNF-α, while upregulating anti-inflammatory cytokines such as IL-10
*IL6↓,
*TNF-α↓,
*IL10↑,
*other↓, This dual action helps to mitigate inflammation in conditions such as arthritis, dermatitis, and inflammatory bowel disease (IBD)
*ROS↓, Aloe Vera polysaccharides exhibit potent antioxidant activity by scavenging reactive oxygen species (ROS) and free radicals,
*SOD↑, The polysaccharides enhance the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), which neutralize oxidative stress and protect cells from damage [17,63].
*Catalase↑,
*GPx↑,
*lipid-P↓, This property is particularly beneficial in preventing lipid peroxidation, DNA damage, and protein oxidation, processes associated with chronic diseases and aging
*DNAdam↓,
*GutMicro↑, Aloe Vera polysaccharides support gastrointestinal health, acting as prebiotics and promoting the growth of beneficial gut microbiota such as Lactobacillus and Bifidobacterium species [64].
*ZO-1↑, enhance the integrity of the intestinal epithelial barrier by upregulating the expression of tight junction proteins such as occludin and zonula occludens-1 (ZO-1) [51,54].
AntiTum↑, Certain polysaccharides in Aloe Vera, including acemannan, have demonstrated antitumoral effects by inducing apoptosis (programmed cell death) in cancer cells.
Casp3↑, This is achieved through the activation of caspase-3 and caspase-9, key enzymes in the apoptotic pathway [45,48].
Casp9↑,
angioG↓, Aloe Vera polysaccharides also inhibit angiogenesis and metastasis by downregulating matrix metalloproteinases (MMPs) and VEGF [75].
MMPs↓,
VEGF↓,
NK cell↑, Moreover, these polysaccharides enhance the immune system’s ability to recognize and destroy cancer cells through stimulating natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) [43,55].

5568- B-Gluc,  immuno,    Beta-glucans in oncology: revolutionizing treatment with immune power & tumor targeting
- Review, Var, NA
TNF-α↓, Beta-glucans suppress pro-inflammatory cytokines (e.g., TNF-α, IL-6) and tumor-promoting pathways like NF-κB, while modulating T-regulatory cells (Tregs) and downregulating PD-L1 to overcome immune evasion.
IL6↓,
NF-kB↓,
PD-L1↓,
Imm↑,
BAX↑, They induce apoptosis via Bax/Bcl-2 regulation, arrest cell cycles at G1/S or G2/M phases, and inhibit angiogenesis by targeting VEGF and MMPs.
Bcl-2↓,
TumCCA↑,
angioG↓,
VEGF↓,
MMPs↓,
OS↑, improved overall survival (OS) in melanoma (hazard ratio
chemoP↑, alongside reduced chemotherapy toxicity
eff↑, Synergy with PD-1/PD-L1 inhibitors enhances immunotherapy efficacy, particularly in immunogenic tumors.
BioAv↑, Advanced nano-delivery systems, including micelles and exosomes, improve bioavailability and tumor targeting.

1532- Ba,    Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives
- Review, NA, NA
ROS↑, Baicalein initially incited the formation of ROS, which subsequently aimed at endoplasmic reticulum stress and stimulated the Ca2+/-reliant mitochondrial death pathway.
ER Stress↑,
Ca+2↑,
MMPs↓,
Cyt‑c↑, cytochrome C release
Casp3↑,
ROS↑, Baicalein on apoptosis in human bladder cancer 5637 cells was investigated, and it was found that it induces ROS generation
DR5↑, Baicalein activates DR5 up-regulation
ROS↑, MCF-7 cells by inducing mitochondrial apoptotic cell death. It does this by producing ROS, such as hydroxyl radicals, and reducing Cu (II) to Cu (I) in the Baicalein–Cu (II) system
BAX↑,
Bcl-2↓,
MMP↓,
Casp3↑,
Casp9↑,
P53↑,
p16↑,
P21↑,
p27↑,
HDAC10↑, modulating the up-regulation of miR-3178 and Histone deacetylase 10 (HDAC10), which accelerates apoptotic cell death
MDM2↓, MDM2-mediated breakdown
Apoptosis↑,
PI3K↓, baicalein-influenced apoptosis is controlled via suppression of the PI3K/AKT axis
Akt↓,
p‑Akt↓, by reducing the concentrations of p-Akt, p-mTOR, NF-κB, and p-IκB while increasing IκB expression
p‑mTOR↓,
NF-kB↓,
p‑IκB↓,
IκB↑,
BAX↑,
Bcl-2↓,
ROS⇅, Based on its metabolic activities and intensity, Baicalein can act as an antioxidant and pro-oxidant.
BNIP3↑, Baicalein also increases the production of BNIP3 which is a protein stimulated by ROS and promotes apoptosis
p38↑,
12LOX↓, inhibition of 12-LOX (Platelet-type 12-Lipoxygenase)
Mcl-1↓,
Wnt?, decreasing Wnt activity
GLI2↓, Baicalein significantly reduced the presence of Gli-2, a crucial transcription factor in the SHH pathway
AR↓, downregulating the androgen receptor (AR)
eff↑, PTX/BAI NE could increase intracellular ROS levels, reduce cellular glutathione (GSH) levels, and trigger caspase-3 dynamism in MCF-7/Tax cells. Moreover, it exhibited higher efficacy in inhibiting tumors in vivo

1524- Ba,    Baicalein Induces Caspase‐dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells
- in-vitro, Lung, A549
DR5↑, Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase‐8
FADD↑,
FasL↑,
Casp8↑,
cFLIP↓, reducing the levels of FLIPs
Casp3↑, activation of caspase‐9 and −3, and cleavage of poly(ADP‐ribose) polymerase
Casp9↑,
cl‑PARP↑,
MMP↓, baicalein caused a mitochondrial membrane potential (MMP),
BID↑, the truncation of Bid (means that the protein has been converted into an active form (tBid) that supports apoptosis.)
Cyt‑c↑, inducing the release of cytochrome c into the cytosol
ROS↑, baicalein increased the generation of reactive oxygen species (ROS)
eff↓, however, an ROS scavenger, N‐acetylcysteine, notably attenuated baicalein‐mediated loss of MMP and activation of caspases
AMPK↑,
Apoptosis↑,
TumCCA↑, sub-G1 phase
DR5↑, baicalein increased the expression of DR5 and FasL in a concentration-dependent manner, whereas the levels of DR4
FasL↑,
DR4∅,
cFLIP↓, baicalein reduced both FLIP(L) and FLIP(S) protein levels
FADD↑, increased FADD expression
MMPs↓, baicalein treatment reduced MMP levels in a concentrationdependent manner

2606- Ba,    Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma
- Review, HCC, NA
ChemoSen↑, In addition, the combination of baicalein and silymarin eradicates HepG2 cells efficiently superior to baicalein or silymarin alone
TumCP↓, Cell viability assays have demonstrated that baicalein is significantly cytotoxic against several HCC cell lines and can inhibit the proliferation of HCC cells through arresting the cell cycle.
TumCCA↑,
TumCMig↓, Baicalein has been proved to inhibit migration and invasion of human HCC cells by reducing the expression and their proteinase activity of matrix metalloproteinases (MMPs),
TumCI↓,
MMPs↓,
MAPK↓, A large number of studies found that baicalein could inhibit migration and invasion of cancer cells by targeting the MAPK, TGF-b/Smad4, GPR30 pathway and molecules such as, ezrin, zinc-finger protein X-linked (ZFX),
TGF-β↓,
ZFX↓,
p‑MEK↓, Baicalein could inhibited the phosphorylation of MEK1 and ERK1/2, leading to decreased expression and proteinase activity of MMP-2/9 and urokinase-type plasminogen activator (u-PA),
ERK↓,
MMP2↓,
MMP9↓,
uPA↓,
TIMP1↓, as well as increased expression of TIMP-1 and TIMP-2
TIMP2↓,
NF-kB↓, Additionally, the nuclear translocation of NF-kB/p50 and p65/RelA and the phosphorylation of I-kappa-B (IKB)-b could be down-regulated by baicalein
p65↓,
p‑IKKα↓,
Fas↑, Hep3 B cells via activating Fas, Caspase -2, -3, -8, -9, down-regulating Bcl-xL, and upregulating Bax [
Casp2↑,
Casp3↑,
Casp8↑,
Casp9↑,
Bcl-xL↓,
BAX↑,
ER Stress↑, baicalein could induced apoptosis via endoplasmic reticulum (ER) stress in SMMC-7721 and Bel-7402
Ca+2↑, increasing intracellular calcium(Ca2+ ), and activating JNK pathwa
JNK↑,
P53↑, selectively induce apoptosis in HCC J5 cells via upregulation of p53
ROS↑, baicalein could induced cell apoptosis through regulating ROS via increasing intracellular H2O 2 level [
H2O2↑,
cMyc↓, baicalein could promote apoptosis in HepG2 and Bel-7402 cells through inhibiting c-Myc and CD24 expression
CD24↓,
12LOX↓, baicalein could induced cell apoptosis in SMMC-7721 and HepG2 cells by specifically inhibiting expression of 12-lipoxygenase(12-LOX), a critical anti-apoptotic genes

2678- BBR,    Berberine as a Potential Agent for the Treatment of Colorectal Cancer
- Review, CRC, NA
*Inflam↓, BBR exerts remarkable anti-inflammatory (94–96), antiviral (97), antioxidant (98), antidiabetic (99), immunosuppressive (100), cardiovascular (101, 102), and neuroprotective (103) activities.
*antiOx↑,
*cardioP↑,
*neuroP↑,
TumCCA↑, BBR could induce G1 cycle arrest in A549 lung cancer cells by decreasing the levels of cyclin D1 and cyclin E1
cycD1/CCND1↓,
cycE/CCNE↓,
CDC2↓, BBR also induced G1 cycle arrest by inhibiting cyclin B1 expression and CDC2 kinase in some cancer cells
AMPK↝, BBR has been suggested to induce autophagy in glioblastoma by targeting the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR)/ULK1 pathway
mTOR↝,
Casp8↑, BBR has been revealed to stimulate apoptosis in leukemia by upregulation of caspase-8 and caspase-9
Casp9↑,
Cyt‑c↑, in skin squamous cell carcinoma A431 cells by increasing cytochrome C levels
TumCMig↓, BBR has been confirmed to inhibit cell migration and invasion by inhibiting the expression of epithelial–mesenchymal transition (EMT)
TumCI↓,
EMT↓,
MMPs↓, metastasis-related proteins, such as matrix metalloproteinases (MMPs) and E-cadherin,
E-cadherin↓,
Telomerase↓, BBR has shown antitumor effects by interacting with microRNAs (125) and inhibiting telomerase activity
*toxicity↓, Numerous studies have revealed that BBR is a safe and effective treatment for CRC
GRP78/BiP↓, Downregulates GRP78
EGFR↓, Downregulates EGFR
CDK4↓, downregulates CDK4, TERT, and TERC
COX2↓, Reduces levels of COX-2/PGE2, phosphorylation of JAK2 and STAT3, and expression of MMP-2/-9.
PGE2↓,
p‑JAK2↓,
p‑STAT3↓,
MMP2↓,
MMP9↓,
GutMicro↑, BBR can inhibit tumor growth through meditation of the intestinal flora and mucosal barrier, and generally and ultimately improve weight loss. BBR has been reported to modulate the composition of intestinal flora and significantly reduce flora divers
eff↝, BBR can regulate the activity of P-glycoprotein (P-gp), and potential drug-drug interactions (DDIs) are observed when BBR is coadministered with P-gp substrates
*BioAv↓, the efficiency of BBR is limited by its low bioavailability due to its poor absorption rate in the gut, low solubility in water, and fast metabolism. Studies have shown that the oral bioavailability of BBR is 0.68% in rats
BioAv↑, combining it with p-gp inhibitors (such as tariquidar and tetrandrine) (196, 198), and modification to berberine organic acid salts (BOAs)

5633- BCA,    Mechanisms Behind the Pharmacological Application of Biochanin-A: A review
- Review, Var, NA - Review, AD, NA
*AntiDiabetic↑, Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action.
*neuroP↑, Biochanin-A has been shown to have a potential neuroprotective impact by modulating multiple critical neurological pathways.
*toxicity↓, Unlike chemical agents such as chemotherapeutic agents, isoflavones have shown zero toxicity to humans
*CYP19↓, Biochanin-A inhibits CYP19 and negatively affects the synthesis of oestrogen in the body which enhances the anti-oestrogenic property in hormone-influenced cancer such as prostate cancer and breast cancer
p‑Akt↓, Biochanin-A inhibits Akt phosphorylation thereby downregulates mTOR signals and disrupts the cell cycle.
mTOR↓,
TumCCA↑,
P21↑, Biochanin-A cause apoptosis in lung cancer by increasing p21, caspase-3, and Bcl-2 levels. It lowers E-cadherin and blocks metastasis.
Casp3↑,
Bcl-2↑,
Apoptosis↑,
E-cadherin↓,
TumMeta↓,
eff↑, The synergism of biochanin-A with 5-fluorouracil evidenced in Caco-2 and HCT-116 cell lines indicates the modulatory influence of biochanin-A in colon cancer treatment.
GSK‐3β↓, It blocked the “Akt and GSK3β phosphorylation and boosted the degradation of β-catenin” ( Mahmoud et al., 2017).
β-catenin/ZEB1↓,
RadioS↑, Biochanin-A when combined with gamma radiation on HT29 cells, which is resistant to radiation, had revealed a reduction in cell proliferation.
ROS↑, Raised levels of ROS, lipid peroxidation, MMP, caspase-3 have been observed more in the treatment group with significant apoptosis
Casp1↑,
MMP2↓, biochanin-A influenced the tumour invasion capacity by lowering matrix-degrading enzymes (MMP 2 and MMP 9) tested in U87MG cells
MMP9↓,
EGFR↓, Biochanin-A by lowering EGFR, p-ERK (Extracellular signal related kinases), p-AKT (Protein kinase-B), c-myc, and MT-MMP1 (Membrane type matrix metalloproteinase) activation, inhibited cell survival.
ChemoSen↑, Biochanin-A synergistically improved temozolomide anti-cancer ability in GBM
PI3K↓, Cell signalling pathways MAP kinase, PI3 kinase, mTOR, matrix metalloproteases, hypoxia-inducible factor, and VEGF were inhibited by biochanin-A, making it suitable in treating GBM
MMPs↓,
Hif1a↓,
VEGF↓,
*ROS↓, anti-diabetic mechanism of biochanin-A is by decreasing oxidative stress
*Obesity↓, strongly suggest that biochanin-A has therapeutic potential in the treatment of obesity and the prevention of cardiovascular disease
*cardioP↑,
*NRF2↑, Biochanin-A up-regulated the Nrf-2 pathway while suppressing the NF-κB cascade,
*NF-kB↓, By activating the Nrf-2 pathway and inhibiting NF-κB activation, biochanin-A may reduce obesity and its related cardiomyopathy by decreasing oxidative stress and inflammation
*Inflam↓,
*lipid-P↓, cardio-protective effects by controlling lipid peroxidation
*hepatoP↑, biochanin-A influence the elevated hepatic enzyme level, such as AST, ALP, ALT, bilirubin, etc., and found to be a promising molecule in hepatotoxicity models
*AST↓,
*ALP↓,
*Bacteria↓, The results indicate that biochanin-A may be an effective alternate to antibiotics for alleviating SARA in cattles
*neuroP↑, the neuroprotective effects of biochanin-A might be attributed to the activation of the Nrf2 pathway and suppression of the NF-κB pathway
*SOD↑, Biochanin-A reduced oxidative stress in the brain by augmenting SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase) and repressing MDA (malondialdehyde) levels.
*GPx↑,
*AChE↓, Acetylcholinesterase activity was found decreased in a dose-reliant manner amongst biochanin-A treated animals
*BACE↓, Biochanin-A non-competitively inhibited BACE1 with an IC 50 value of 28 μM.
*memory↑, estore learning and memory deficits in ovariectomized (OVX) rats.
*BioAv↓, The bioavailability of biochanin-A is poor.

5634- BCA,    Molecular Mechanisms of Biochanin A in AML Cells: Apoptosis Induction and Pathway-Specific Regulation in U937 and THP-1
- in-vitro, AML, U937 - in-vitro, AML, THP1
Apoptosis↑, Biochanin A induced dose-dependent apoptosis, as evidenced by caspase-7 activation and PARP1 cleavage.
Casp7↑,
PARP1↑,
Bcl-2↓, Biochanin A downregulated oncogenes such as RUNX1, BCL2, and MYC while upregulating CHOP (GADD153), CDKN1A (p21), and SQSTM1 (p62), contributing to apoptosis and cell cycle arrest across both cell lines.
Myc↓,
CHOP↑,
P21↑,
p62↑,
TumCCA↑,
TXNIP↑, In contrast, in U937 cells, Biochanin A upregulated TXNIP and downregulated CCND2, highlighting the involvement of oxidative stress and G1/S cell cycle arrest.
ROS↑,
*antiOx↑, Biochanin A exhibits a broad spectrum of biological activities, including antioxidant, anti-inflammatory, estrogenic, metabolic regulatory, neuroprotective, and anticancer effects [1].
*Inflam↓,
*neuroP↑,
AntiCan↑,
TumCP↓, The anticancer mechanisms of Biochanin A involve the inhibition of cell proliferation via the modulation of cyclins and cyclin-dependent kinases
angioG↓, inhibition of angiogenesis and metastasis through downregulation of VEGF and matrix metalloproteinases (MMPs), and activation of apoptosis
TumMeta↓,
VEGF↓,
MMPs↓,
tumCV↓, Biochanin A significantly inhibited cell viability at concentrations ≥100 μM in U937 cells and ≥50 μM in THP-1 cells
DNAdam↑, Biochanin A induces a DNA damage response
CHOP↑, In our study, we observed a significant induction of CHOP protein expression following treatment with Biochanin A at concentrations of 100 μM and 200 μM.
cMyc↓, Biochanin A inhibited c-Myc protein expression in U937 and THP-1 cells
BioAv↓, Biochanin A remains limited due to its poor aqueous solubility and rapid systemic clearance, which render the 100–200 μM concentrations used in this study difficult to achieve in vivo
Half-Life↓,
BioAv↑, PEG-NLC formulations have been shown to significantly increase the plasma half-life and bioavailability of flavonoids

2737- BetA,    Multiple molecular targets in breast cancer therapy by betulinic acid
- Review, Var, NA
TumCP↓, Betulinic acid (BA), a pipeline anticancer drug, exerts anti-proliferative effects on breast cancer cells is mainly through inhibition of cyclin and topoisomerase expression, leading to cell cycle arrest.
Cyc↓,
TOP1↓,
TumCCA↑,
angioG↓, anti-angiogenesis effect by inhibiting the expression of transcription factor nuclear factor kappa B (NF-κB), specificity protein (Sp) transcription factors, and vascular endothelial growth factor (VEGF) signaling.
NF-kB↓, Inhibition of NF-kB signaling pathway
Sp1/3/4↓,
VEGF↓,
MMPs↓, inhibiting the expression of matrix metalloproteases
ChemoSen↑, Synergistically interactions of BA with other chemotherapeutics are also described in the literature.
eff↑, BA is highly lipid soluble [74,75], and it readily passes through membranes, including plasma and mitochondrial membranes. BA acts directly on mitochondria
MMP↓, decreases mitochondrial outer membrane potential (MOMP), leading to increased outer membrane permeability, generation of reactive oxygen species (ROS),
ROS↑,
Bcl-2↓, reducing expression of anti-apoptotic proteins Bcl-2, Bcl-XL and Mcl-1
Bcl-xL↓,
Mcl-1↓,
lipid-P↑, BA inhibits the growth of breast cancer cells via lipid peroxidation resulting from the generation of ROS
RadioS↑, The cytotoxicity effect of BA on glioblastoma cells is not strong; however, some studies indicate that the combination of BA and radiotherapy could represent an advancement in treatment of glioblastoma [
eff↑, BA and thymoquinone inhibit MDR and induce cell death in MCF-7 breast cancer cells by suppressing BCRP [

2742- BetA,    Betulinic acid impairs metastasis and reduces immunosuppressive cells in breast cancer models
- in-vitro, BC, MDA-MB-231 - in-vivo, BC, 4T1 - in-vitro, BC, MCF-7
tumCV↓, BA decreased the viability of three breast cancer cell lines and markedly impaired cell migration and invasion
TumCMig↓,
TumCI↓,
STAT3↑, BA could inhibit the activation of stat3 and FAK which resulted in a reduction of matrix metalloproteinases (MMPs)
FAK↓,
MMPs↓,
MMP2↓, BA treatment decreased the expression of MMP-2 and MMP-9 while increased the expression of TIMP-2 in 4T1 and MDA-MB-231 cells.
MMP9↓,
TIMP2↑,

2773- Bos,    Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: Potential role in prevention and therapy of cancer
- Review, Var, NA
Inflam↓, BA has been shown to be effective against chronic inflammation-driven diseases such as adjuvant or bovine serum albumin-induced arthritis, osteoarthritis, Crohn’s disease, ulcerative colitis, and ileitis, and galactosamine/endotoxin-induced hepa
TumCCA↑, BA induced apoptosis was mediated by cell cycle arrest in the G1 phase and by activating caspases 3, 8 and 9 in HT-29 cells
Casp3↑,
Casp8↑,
Casp9↑,
STAT3↑, BA inhibited the growth of multiple myeloma cells by suppression of STAT3 pathway and by activation of protein tyrosine phosphatase SHP1
SHP1↓,
NF-kB↓, BA down regulated the expression of NF-kB, cyclin D1, COX2, Ki-67, CD-31 and IAPs in the tumor tissue.
cycD1/CCND1↓,
COX2↓,
Ki-67↓,
CD31↓,
IAP1↓,
MMPs↓, AKBA induced cell cycle arrest was mediated by down-regulating the expression of cyclinD1, suppresses MMP activity, and also induced apoptosis by suppressing Bcl-2, and Bcl-xL expression
Bcl-2↓,
Bcl-xL↓,

5868- CA,    Carnosic acid inhibits the proliferation and migration capacity of human colorectal cancer cells
- in-vitro, Colon, Caco-2 - in-vitro, Colon, HT29 - in-vitro, CRC, LoVo
Apoptosis↑, CA induced cell death by apoptosis in Caco-2 line after 24 h of treatment and inhibited cell adhesion and migration,
TumCMig↓, Inhibition of cell migration by CA
uPA↓, possibly by reducing the activity of secreted proteases such as urokinase plasminogen activator (uPA) and metalloproteinases (MMPs).
MMPs↓,
COX2↓, we have determined that CA downregulates the expression of COX-2 in Caco-2 cells at both the mRNA and protein levels.
TumCA↓, Inhibition of cell adhesion by CA
MMP9↓, CA treatment after 24 h decreased Caco-2 conditioned media uPA activity and MMP-9 and MMP-2.
MMP2↓,
chemoPv↑, CA may serve as chemopreventive and/or chemotherapeutic agent against colorectal cancer progress.

5767- CAPE,    Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer
- Review, Oral, NA
TumCP↓, CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells.
tumCV↓,
TumMeta↓,
Akt↓, CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2).
NF-kB↓,
MMPs↓,
EGFR↓,
COX2↓,
TumCCA?, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells.

5763- CAPE,    Synthesis and Biological Evaluation of a Caffeic Acid Phenethyl Ester Derivatives as Anti-Hepatocellular Carcinoma Agents via Inhibition of Mitochondrial Respiration and Disruption of Cellular Metabolism
- NA, HCC, NA
*antiOx↑, Caffeic acid phenethyl ester (CAPE, Scheme 1), a key bioactive constituent of propolis, has been established to possess a range of significant biological properties [29], including antioxidant [30,31], anti-inflammatory [32], and neuroprotective effe
*neuroP↑,
NF-kB↓, significant inhibitory effect on the NF-κB signaling pathway,
TumCG↓, CAPE has also been reported to suppress tumor growth and metastasis by modulating multiple signaling pathways,
TumMeta↓,
MMPs↓, including the inhibition of matrix metalloproteinases (MMPs), suppression of p53 ubiquitination and degradation [41]
P53↑,
ChemoSen↑, CAPE can act synergistically with conventional chemotherapeutic agents

5908- CAR,    Carvacrol improves neurological function by inhibiting TRPM7-mediated BBB disruption and hemorrhage after TBI
- in-vivo, Nor, NA
*TRPM7↓, carvacrol, a TRPM7 inhibitor
*BBB↑, Carvacrol treatment significantly attenuated BBB disruption and hemorrhage, preserved tight junction proteins
*motorD↑, Behaviorally, carvacrol improved neurological scores, motor performance, and cognitive function after TBI.
*cognitive↑, Carvacrol improves motor and cognitive function after TBI
*Dose↝, Carvacrol was administered at a dose of 50 mg/kg immediately and 8 h after TBI
MMPs↓, Carvacrol prevents loss of tight junction proteins by attenuating MMPs expression and activity after TBI

4762- CoQ10,    The role of coenzyme Q10 as a preventive and therapeutic agent for the treatment of cancers
- Review, Var, NA
*AntiCan↓, Coenzyme Q10 (CoQ10) is a naturally occurring component that performs an anticancer function by reducing oxidative stress.
*ROS↓,
chemoPv↑, As a defensive mechanism against oxidative stress elevation in the antioxidative level including CoQ10 is expected, and an increase in these agents can protect cells and organs from side effects of chemotherapeutic drugs.
TumCCA↑, CoQ10 may induce its antitumor effect through multiple mechanisms, including anti-oxidation, anti-inflammation, cell cycle arrest, promoting apoptosis, reducing cell proliferation, inhibiting angiogenesis, suppression of MMPs, and so on
Apoptosis↑,
TumCP↓,
angioG↓,
MMPs↓,
ChemoSen∅, The review points out that: Some studies show improved tolerance without reduced response (chatAI interpretation)

4769- CoQ10,    CoQ10 Is Key for Cellular Energy and Cancer Support
- Review, Var, NA
Risk↓, CoQ10, an essential compound for cellular energy production, is often found at low levels in cancer patients, suggesting a link between CoQ10 deficiency and cancer risk
TumCG↓, Research shows CoQ10 helps fight cancer by slowing tumor growth, preventing new blood vessel formation in tumors and triggering self-destruction of abnormal cells
angioG↓,
TumCD↑,
*toxicity↓, The compound helps regulate immune function and inflammation by supporting mitochondrial health and enhancing T-cell activity, while showing minimal side effects even at high doses
*BioAv↑, Simple steps, like splitting doses and pairing CoQ10 with a meal containing fats, aid in its absorption and effectiveness
MMPs↓, reported ability of CoQ10 to suppress something known as MMPs (matrix metalloproteinases)
Inflam↓, A further aspect focused on the anti-inflammatory effects of CoQ10
chemoP↑, Some individuals received significant help in diminishing tumor markers, while others used CoQ10 to mitigate drug side effects.
cardioP↑, According to the authors, coenzyme Q10 shows evidence of lowering that heart strain.
*ROS↓, Researchers explained that coenzyme Q10 is a compound naturally made in your body, essential for mitochondrial energy production and normal oxidative processes
*toxicity↝, Liver enzyme elevation has been reported after prolonged use of doses of 300 milligrams (mg) daily, but this effect did not escalate into overt liver damage.
Dose?, If you have never taken CoQ10 before, aim for 200 mg to 300 mg daily for the first three weeks. After about 21 days, step down to 100 mg daily

3583- CUR,    Curcumin: an orally bioavailable blocker of TNF and other pro-inflammatory biomarkers
- Review, Arthritis, NA
*TNF-α↓, Curcuma longa) that is very inexpensive, orally bioavailable and highly safe in humans, yet can block TNF-α action and production in in vitro models, in animal models and in humans
*IL1β↓, curcumin has been found to down-regulate the expression of TNF-α and IL-1β in ankle joints and decrease NF-κB activity, PGE2 production, COX-2 expression and MMP secretion in synoviocytes.
*NF-kB↓,
*PGE2↓,
*COX2↓,
*MMPs↓,
*eff↑, curcumin has been shown to have a synergistic effect with methotrexate in decreasing adjuvant-induced arthritis in mice

13- CUR,    Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action
- Review, BC, NA
P53↑, upregulated other targets including p53, death receptor (DR-5), JN-kinase, Nrf-2, and peroxisome proliferator-activated receptor γ (PPARγ) factors
DR5↑,
JNK↑,
NRF2↑,
PPARγ↑,
HER2/EBBR2↓, (Her-2, IR, ER-a, and Fas receptor)
IR↓,
ER(estro)↓,
Fas↑,
PDGF↓, (PDGF, TGF, FGF, and EGF)
TGF-β↓,
FGF↓,
EGFR↓,
JAK↓,
PAK↓,
MAPK↓,
ATPase↓, (ATPase, COX-2, and matrix metalloproteinase enzyme [MMP])
COX2↓,
MMPs↓,
IL1↓, inflammatory cytokines (IL-1, IL-2, IL-5, IL-6, IL-8, IL-12, and IL-18)
IL2↓,
IL5↓,
IL6↓,
IL8↓,
IL12↓,
IL18↓,
NF-kB↓,
NOTCH1↓,
STAT1↓,
STAT4↓,
STAT5↓,
STAT3↓,

4826- CUR,    The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management
- Review, Var, NA
*antiOx↑, Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators
*Inflam↑,
*ROS↓,
Apoptosis↑, Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers
TumCP↓,
BioAv↓, application is limited by its poor bioavailability due to its rapid metabolism and low absorption.
Half-Life↓,
eff↑, curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy.
TumCCA↑, Studies have demonstrated that curcumin can suppress the proliferation of cancer cells by interfering with the cell cycle [21,22]
BAX↑, Curcumin enhances the expression of pro-apoptotic proteins such as Bax, Bak, PUMA, Bim, and Noxa and death receptors such as TRAIL-R1/DR4 and TRAIL-R2/DR5
Bak↑,
PUMA↑,
BIM↑,
NOXA↑,
TRAIL↑,
Bcl-2↓, curcumin decreases the levels of anti-apoptotic proteins like Bcl-2, Bcl-XL, survin, and XIAP
Bcl-xL↓,
survivin↓,
XIAP↓,
cMyc↓, This shift in the balance of apoptotic regulators facilitates the release of cytochrome c from mitochondria [33,35] and activates caspases
Casp↑,
NF-kB↓, Curcumin suppresses the activity of key transcription factors like NF-κB, STAT3, and AP-1 and interferes with critical signal transduction pathways such as PI3K/Akt/mTOR and MAPK/ERK.
STAT3↓,
AP-1↓,
angioG↓, curcumin inhibits angiogenesis and metastasis by downregulating VEGF, VEGFR2, and matrix metalloproteinases (MMPs).
TumMeta↑,
VEGF↓,
MMPs↓,
DNMTs↓, Epigenetic modifications through the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) further contribute to its anticancer properties.
HDAC↓,
ROS↑, curcumin-loaded nanoparticles showed significant cytotoxicity in the SCC25, MDA-MB-231, and A549 cell lines, with a decrease in tumor cell proliferation, an increase in ROS, and an increase in apoptosis.

1854- dietFMD,    How Far Are We from Prescribing Fasting as Anticancer Medicine?
- Review, Var, NA
ChemoSideEff↓, ample nonclinical evidence indicating that fasting can mitigate the toxicity of chemotherapy and/or increase the efficacy of chemotherapy.
ChemoSen↑, Fasting-Induced Increase of the Efficacy of Chemotherapy
IGF-1↓,
IGFBP1↑, biological activity of IGF-1 is further compromised due to increased levels of insulin-like growth factor binding protein 1 (IGFBP1)
adiP↑, increased levels of adiponectin stimulate the fatty acid breakdown.
glyC↓, After depletion of stored glycogen, which occurs usually 24 h after initiation of fasting, the fatty acids serve as the main fuels for most tissues
E-cadherin↑, upregulation of E-cadherin expression via activation of c-Src kinase
MMPs↓, decrease of cytokines, chemokines, metalloproteinases, growth factors
Casp3↑, increase of level of activated caspase-3
ROS↑, it is postulated that the beneficial effects of fasting are ascribed to rapid metabolic and immunological response, triggered by a temporary increase in oxidative free radical production
ATP↓, Glucose deprivation leads to ATP depletion, resulting in ROS accumulation
AMPK↑, Additionally, ROS activate AMPK
mTOR↓, Under conditions of glucose deprivation, AMPK inhibits mTORC1
ROS↑, Beyond glucose deprivation, another mechanism increasing ROS levels is the AA (amino acids) starvation
Glycolysis↓, Indeed, in cancer cells, limited glucose sources impair glycolysis, decrease glycolysis-based NADPH production due to reduced utilization of the pentose phosphate pathway [88,89,90,91],
NADPH↓,
OXPHOS↝, and shift the metabolism from glycolysis to oxidative phosphorylation (OXPHOS) (“anti-Warburg effect”), leading to ROS overload [92,93,94,95].
eff↑, Fasting compared to long-term CR causes a more profound decrease in insulin (90% versus 40%, respectively) and blood glucose (50% versus 25%, respectively).
eff↑, FMD have been demonstrated to result in alterations of the serum levels of IGF-I, IGFBP1, glucose, and ketone bodies reminiscent of those observed in fasting
*RAS↓, A plausible explanation of the differential protective effect of fasting against chemotherapy is the attenuation of the Ras/MAPK and PI3K/Akt pathways downstream of decreased IGF-1 in normal cells
*MAPK↓,
*PI3K↓,
*Akt↓,
eff↑, Starvation combined with cisplatin has been shown in vitro to protect normal cells, promoting complete arrest of cellular proliferation mediated by p53/p21 activation in AMPK-dependent and ATM-independent manner
ROS↑, generation of ROS due to paradoxical activation of the AKT/S6K, partially via the AMPK-mTORC1 energy-sensing pathways malignant cells
Akt↑, cancer cells
Casp3↑, combination of fasting and chemotherapy was in part ascribed to enhanced apoptosis due to activation of caspase 3

3201- EGCG,    Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential
- Review, NA, NA
*AntiCan↑, EGCG’s therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes
*cardioP↑,
*neuroP↑,
*BioAv↝, Factors such as fasting, storage conditions, albumin levels, vitamin C, fish oil, and piperine have been shown to affect plasma concentrations and the overall bioavailability of EGCG
*BioAv↓, Conversely, bioavailability is reduced by processes such as air oxidation, sulfation, glucuronidation, gastrointestinal degradation, and interactions with Ca2+, Mg2+, and trace metals,
*BioAv↓, EGCG’s oral bioavailability is generally low, with marked differences observed across species, for example, bioavailability rates of 26.5% in CF-1 mice and just 1.6% in Sprague Dawley rats
*Dose↝, plasma concentrations exceeded 1 μM only when doses of 1 g or higher were administered.
*Half-Life↝, Specifically, a dose of 1600 mg yielded a Cmax of 3392 ng/mL (range: 130–3392 ng/mL), with peak levels observed between 1.3 and 2.2 h, AUC (0–∞) values ranging from 442 to 10,368 ng·h/mL, and a half-life (t1/2z) of 1.9 to 4.6 h.
*BioAv↑, Studies on the distribution of EGCG have revealed that, despite its limited absorption, it is rapidly disseminated throughout the body or quickly converted into metabolites
*BBB↑, Additionally, EGCG can cross the blood–brain barrier, allowing it to reach the brain
*hepatoP↓, Several studies have documented liver damage linked to green tea consumption [48,49,50,51,52,53].
*other↓, EGCG has also been shown to inhibit the intestinal absorption of non-heme iron in a dose-dependent manner in a controlled clinical trial
*Inflam↓, EGCG has been widely recognized for its anti-inflammatory effects
*NF-kB↓, EGCG has been shown to suppress NF-κB activation, inhibit its nuclear translocation, and block AP-1 activity
*AP-1↓,
*iNOS↓, downregulation of pro-inflammatory enzymes like iNOS and COX-2 and scavenging of ROS/RNS, including nitric oxide and peroxynitrite
*COX2↓,
*ROS↓,
*RNS↓,
*IL8↓, EGCG has been shown to suppress airway inflammation by reducing IL-8 release, a cytokine involved in neutrophil aggregation and ROS production.
*JAK↓, EGCG blocks the JAK1/2 signaling pathway
*PDGFR-BB↓, downregulate PDGFR and IGF-1R gene expression
*IGF-1R↓,
*MMP2↓, reduce MMP-2 mRNA expression
*P53↓, downregulation of the p53-p21 signaling pathway and the enhanced expression of Nrf2
*NRF2↑,
*TNF-α↓, 25 to 100 μM reduced the levels of TNF-α, IL-6, and ROS while enhancing the expression of E2F2 and superoxide dismutases (SOD1 and SOD2), enzymes vital for cellular antioxidant defense.
*IL6↓,
*E2Fs↑,
*SOD1↑,
*SOD2↑,
Casp3↑, EGCG has been shown to activate key apoptotic pathways, such as caspase-3 activation, cytochrome c release, and PARP cleavage, in various cell models, including PC12 cells exposed to oxidative stress
Cyt‑c↑,
PARP↑,
DNMTs↓, (1) the inhibition of DNA hypermethylation by blocking DNA methyltransferase (DNMT)
Telomerase↓, (2) the repression of telomerase activity;
Hif1a↓, (3) the suppression of angiogenesis via the inhibition of HIF-1α and NF-κB;
MMPs↓, (4) the prevention of cellular metastasis by inhibiting matrix metalloproteinases (MMPs);
BAX↑, (5) the promotion of apoptosis through the activation of pro-apoptotic proteins like BAX and BAK
Bak↑,
Bcl-2↓, while downregulating anti-apoptotic proteins like BCL-2 and BCL-XL;
Bcl-xL↓,
P53↑, (6) the upregulation of tumor suppressor genes such as p53 and PTEN;
PTEN↑,
TumCP↓, (7) the inhibition of inflammation and proliferation via NF-κB suppression;
MAPK↓, (8) anti-proliferative activity through the modulation of MAPK and IGF1R pathways
HGF/c-Met↓, EGCG inhibits hepatocyte growth factor (HGF), which is involved in tumor migration and invasion
TIMP1↑, EGCG has also been shown to influence the expression of tissue inhibitors of metalloproteinases (TIMPs) and MMPs, which are involved in tumorigenesis
HDAC↓, nhibition of UVB-induced DNA hypomethylation and modulation of DNMT and histone deacetylase (HDAC) activities
MMP9↓, inhibiting MMPs such as MMP-2 and MMP-9
uPA↓, EGCG may block urokinase-like plasminogen activator (uPA), a protease involved in cancer progression
GlutMet↓, EGCG can exert antitumor effects by inhibiting glycolytic enzymes, reducing glucose metabolism, and further suppressing cancer-cell growth
ChemoSen↑, EGCG’s combination with standard chemotherapy drugs may enhance their efficacy through additive or synergistic effects, while also mitigating chemotherapy-related side effects
chemoP↑,

1503- EGCG,    Epigenetic targets of bioactive dietary components for cancer prevention and therapy
- Review, NA, NA
selectivity↑, EGCG has been shown to induce apoptosis and cell cycle arrest in many cancer cells without affecting normal cells
DNMT1↓, inhibition of DNMT1 leading to demethylation and reactivation of methylation-silenced genes.
RECK↑, EGCG-induced epigenetic reactivation of RECK
MMPs↓, negatively regulates matrix metalloproteinases (MMPs)
TumCI↓, inhibits tumor invasion, angiogenesis, and metastasis
angioG↓,
TumMeta↓,
HATs↓, EGCG has strong HAT inhibitory activity
IκB↑, increases the level of cytosolic IκBα
NF-kB↓, suppresses tumor necrosis factor α-induced NF-κB activation
IL6↓,
COX2↓,
NOS2↓,
ac‑H3↑, increased the levels of acetylated histone H3 (LysH9/18) and H4 levels
ac‑H4↑,
eff↑, EGCG may synergize with the HDAC inhibitory action of vorinostat to help de-repress silenced tumor suppressor genes regulating key functions such as proliferation and cell survival

1516- EGCG,    Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential
- Review, NA, NA
*Dose∅, A pharmacokinetic study in healthy individuals receiving single doses of EGCGrevealed that plasma concentrations exceeded 1 μM only with doses of >1 g
Half-Life∅, peak levels observed between 1.3 and 2.2 h (and a half-life (t1/2z) of 1.9 to 4.6 h)
BioAv∅, oral bioavailability of 20.3% relative to intravenous admistration
BBB↑, EGCG can cross the blood–brain barrier, allowing it to reach the brain
toxicity∅, Isbrucher et al. found no evidence of genotoxicity in rats following oral administration of EGCG at doses of 500, 1000, or 2000 mg/kg, or intravenous injections of 10, 25, or 50 mg/kg/day.
eff↓, interaction with the folate transporter has been reported, leading to reduced bioavailability of folic acid
Apoptosis↑,
Casp3↑,
Cyt‑c↑, cytochrome c release
cl‑PARP↑,
DNMTs↓,
Telomerase↓,
angioG↓,
Hif1a↓,
NF-kB↓,
MMPs↓,
BAX↑,
Bak↑,
Bcl-2↓,
Bcl-xL↓,
P53↑,
PTEN↑,
IGF-1↓,
H3↓,
HDAC1↓,
*LDH↓, reduces LDL cholesterol, decreases oxidative stress by neutralizing ROS
*ROS↓,

2992- EGCG,    Effects of Epigallocatechin-3-Gallate on Matrix Metalloproteinases in Terms of Its Anticancer Activity
- Review, Var, NA
AP-1↓, MMPs have binding sites for at least one transcription factor of AP-1, Sp1, and NF-κB, and EGCG can downregulate these transcription factors through signaling pathways mediated by reactive oxygen species
Sp1/3/4↓,
NF-kB↓,
ERK↓, EGCG can also decrease nuclear ERK, p38, heat shock protein-27 (Hsp27), and β-catenin levels, leading to suppression of MMPs’ expression.
P-gp↓,
HSP27↓,
β-catenin/ZEB1↓,
MMPs↓,
TNF-α↓, suppress the production of inflammatory cytokines such as TNFα and IL-1β.
IL1β↓,
MMP2↓, EGCG inhibited MMP2 secretion in glioblastoma cells.

2827- FIS,    The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
- Review, Var, NA
*antiOx↑, effective antioxidant, anti-inflammatory
*Inflam↓,
neuroP↑, neuro-protective, anti-diabetic, hepato-protective and reno-protective potential.
hepatoP↑,
RenoP↑,
cycD1/CCND1↓, Figure 3
TumCCA↑,
MMPs↓,
VEGF↓,
MAPK↓,
NF-kB↓,
angioG↓,
Beclin-1↑,
LC3s↑,
ATG5↑,
Bcl-2↓,
BAX↑,
Casp↑,
TNF-α↓,
Half-Life↓, Fisetin was given at an effective dosage of 223 mg/kilogram intraperitoneally in mice. The plasma concentration declined biophysically, with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h,
MMP↓, Fisetin powerfully improved apoptotic cells and caused the depolarization of the mitochondrial membrane.
mt-ROS↑, Fisetin played a role in the induction of apoptosis, independently of p53, and increased mitochondrial ROS generation.
cl‑PARP↑, fisetin-induced sub-G1 population as well as PARP cleavage.
CDK2↓, Moreover, the activities of cyclin-dependent kinases (CDK) 2 as well as CDK4 were decreased by fisetin and also inhibited CDK4 activity in a cell-free system, demonstrating that it might directly inhibit the activity of CDK4
CDK4↓,
Cyt‑c↑, Moreover, release of cytochrome c and Smac/Diablo was induced by fisetin
Diablo↑,
DR5↑, Fisetin caused an increase in the protein levels of cleaved caspase-8, DR5, Fas ligand, and TNF-related apoptosis-inducing ligand
Fas↑,
PCNA↓, Fisetin decreased proliferation-related proteins such as PCNA, Ki67 and phosphorylated histone H3 (p-H3) and decreased the expression of cell growth
Ki-67↓,
p‑H3↓,
chemoP↑, Paclitaxel treatment only showed more toxicity to normal cells than the combination of flavonoids with paclitaxel, suggesting that fisetin might bring some safety against paclitaxel-facilitated cytotoxicity.
Ca+2↑, Fisetin encouraged apoptotic cell death via increased ROS and Ca2+, while it increased caspase-8, -9 and -3 activities and reduced the mitochondrial membrane potential in HSC3 cells.
Dose↝, After fisetin treatment at 40 µM, invasion was reduced by 87.2% and 92.4%, whereas after fisetin treatment at 20 µM, invasion was decreased by 52.4% and 59.4% in SiHa and CaSki cells, respectively
CDC25↓, This study proposes that fisetin caused the arrest of the G2/M cell cycle via deactivating Cdc25c as well Cdc2 via the activation of Chk1, 2 and ATM
CDC2↓,
CHK1↑,
Chk2↑,
ATM↑,
PCK1↓, fisetin decreases the levels of SOS-1, pEGFR, GRB2, PKC, Ras, p-p-38, p-ERK1/2, p-JNK, VEGF, FAK, PI3K, RhoA, p-AKT, uPA, NF-ĸB, MMP-7,-9 and -13, whereas it increases GSK3β as well as E-cadherin in U-2 OS
RAS↓,
p‑p38↓,
Rho↓,
uPA↓,
MMP7↓,
MMP13↓,
GSK‐3β↑,
E-cadherin↑,
survivin↓, whereas those of survivin and BCL-2 were reduced in T98G cells
VEGFR2↓, Fisetin inhibited the VEGFR expression in Y79 cells as well as the angiogenesis of a tumor.
IAP2↓, The downregulation of cIAP-2 by fisetin
STAT3↓, fisetin induced apoptosis in TPC-1 cells via the initiation of oxidative damage and enhanced caspases expression by downregulating STAT3 and JAK 1 signaling
JAK1↓,
mTORC1↓, Fisetin acts as a dual inhibitor of mTORC1/2 signaling,
mTORC2↓,
NRF2↑, Moreover, In JC cells, the Nrf2 expression was gradually increased by fisetin from 8 h to 24 h

2868- HNK,    Honokiol: A review of its pharmacological potential and therapeutic insights
- Review, Var, NA - Review, Sepsis, NA
*P-gp↓, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6),
*ROS↓,
*TNF-α↓,
*IL10↓,
*IL6↓,
eIF2α↑, Bcl-2, phosphorylated eIF2α, CHOP,GRP78, Bax, cleaved caspase-9 and phosphorylated PERK
CHOP↑,
GRP78/BiP↑,
BAX↑,
cl‑Casp9↑,
p‑PERK↑,
ER Stress↑, endoplasmic reticulum stress and proteins in apoptosis in 95-D and A549 cells
Apoptosis↑,
MMPs↓, decrease in levels of matrix metal-mloproteinases, P-glycoprotein expression, the formation of mammosphere, H3K27 methyltransferase, c-FLIP, level of CXCR4 receptor,pluripotency-factors, Twist-1, class I histone deacetylases, steroid receptor co
cFLIP↓,
CXCR4↓,
Twist↓,
HDAC↓,
BMPs↑, enhancement in Bax protein, and (BMP7), as well as interference with an activator of transcription 3 (STAT3), (mTOR), (EGFR), (NF-kB) and Shh
p‑STAT3↓, secreased the phosphorylation of STAT3
mTOR↓,
EGFR↓,
NF-kB↓,
Shh↓,
VEGF↓, induce apoptosis, and regulate the vascular endothelial growth factor-A expression (VEGF-A)
tumCV↓, human glioma cell lines (U251 and U-87 MG) through inhibition of colony formation, glioma cell viability, cell migration, invasion, suppression of ERK and AKT signalling cascades, apoptosis induction, and reduction of Bcl-2 expression.
TumCMig↓,
TumCI↓,
ERK↓,
Akt↓,
Bcl-2↓,
Nestin↓, increased the Bax expression, lowered the CD133, EGFR, and Nesti
CD133↓,
p‑cMET↑, HKL through the downregulating the phosphorylation of c-Met phosphorylation and stimulation of Ras,
RAS↑,
chemoP↑, Cheng and coworker determined the chemopreventive role of HKL against the proliferation of renal cell carcinoma (RCC) 786‑0 cells through multiple mechanism
*NRF2↑, , HKL also effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in in vivo and in vitro model
*NADPH↓, (HUVECs) such as inhibition of NADPH oxidase activity, suppression of p22 (phox) protein expression, Rac-1 phosphorylation, reactive oxygen species production, inhibition of degradation of Ikappa-B-alpha, and suppression of activity of of NF-kB
*p‑Rac1↓,
*ROS↓,
*IKKα↑,
*NF-kB↓,
*COX2↓, Furthermore, HKL treatment the inhibited cyclooxygenase (COX-2) upregulation, reduces prostaglandin E2 production, enhanced caspase-3 activity reduction
*PGE2↓,
*Casp3↓,
*hepatoP↑, compound also displayed hepatoprotective action against oxidative injury in tert-butyl hydroperoxide (t-BHP)-injured AML12 liver cells in in vitro model
*antiOx↑, compound reduces the level of acetylation on SOD2 to stimulate its antioxidative action, which results in reduced reactive oxygen species aggregation in AML12 cells
*GSH↑, HKL prevents oxidative damage induced by H2O2 via elevating antioxidant enzymes levels which includes glutathione and catalase and promotes translocation and activation transcription factor Nrf2
*Catalase↑,
*RenoP↑, imilarly, the compound protects renal reperfusion/i-schemia injury (IRI) in adult male albino Wistar rats via reducing theactivities of serum alkaline phosphatase (ALP), aspartate aminotrans- ferase (AST) and alanine aminotransferase (ALT)
*ALP↓,
*AST↓,
*ALAT↓,
*neuroP↑, Several reports and works have shown that HKL displays some neuroprotective properties
*cardioP↑, Cardioprotection
*HO-1↑, the expression level of heme oxygenase-1 (HO-1)was remarkably up-regulated and miR-218-5p was significantly down-regulated in septic mice treated with HKL
*Inflam↓, anti-inflammatory action of HKL at dose of 10 mg/kg in the muscle layer of mice

2864- HNK,    Honokiol: A Review of Its Anticancer Potential and Mechanisms
- Review, Var, NA
TumCCA↑, induction of G0/G1 and G2/M cell cycle arrest
CDK2↓, (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins),
EMT↓, epithelial–mesenchymal transition inhibition via the downregulation of mesenchymal markers
MMPs↓, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases
AMPK↑, (activation of 5′ AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling)
TumCI↓, inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)
TumCMig↓,
TumMeta↓,
VEGFR2↓,
*antiOx↑, diverse biological activities, including anti-arrhythmic, anti-inflammatory, anti-oxidative, anti-depressant, anti-thrombocytic, and anxiolytic activities
*Inflam↓,
*BBB↑, Due to its ability to cross the blood–brain barrier
*neuroP↑, beneficial towards neuronal protection through various mechanism, such as the preservation of Na+/K+ ATPase, phosphorylation of pro-survival factors, preservation of mitochondria, prevention of glucose, reactive oxgen species (ROS), and inflammatory
*ROS↓,
Dose↝, Generally, the concentrations used for the in vitro studies are between 0–150 μM
selectivity↑, Interestingly, honokiol has been shown to exhibit minimal cytotoxicity against on normal cell lines, including human fibroblast FB-1, FB-2, Hs68, and NIH-3T3 cells
Casp3↑, ↑ Caspase-3 & caspase-9
Casp9↑,
NOTCH1↓, Inhibition of Notch signalling: ↓ Notch1 & Jagged-1;
cycD1/CCND1↓, ↓ cyclin D1 & c-Myc;
cMyc↓,
P21?, ↑ p21WAF1 protein
DR5↑, ↑ DR5 & cleaved PARP
cl‑PARP↑,
P53↑, ↑ phosphorylated p53 & p53
Mcl-1↑, ↓ Mcl-1 protein
p65↓, ↓ p65; ↓ NF-κB
NF-kB↓,
ROS↑, ↑ JNK activation ,Increase ROS activity:
JNK↑,
NRF2↑, ↑ Nrf2 & c-Jun protein activation
cJun↑,
EF-1α↓, ↓ EFGR; ↓ MAPK/PI3K pathway activity
MAPK↓,
PI3K↓,
mTORC1↓, ↓ mTORC1 function; ↑ LKB1 & cytosolic localisation
CSCs↓, Inhibit stem-like characteristics: ↓ Oct4, Nanog & Sox4 protein; ↓ STAT3;
OCT4↓,
Nanog↓,
SOX4↓,
STAT3↓,
CDK4↓, ↓ Cdk2, Cdk4 & p-pRbSer780;
p‑RB1↓,
PGE2↓, ↓ PGE2 production ↓ COX-2 ↑ β-catenin
COX2↓,
β-catenin/ZEB1↑,
IKKα↓, ↓ IKKα
HDAC↓, ↓ class I HDAC proteins; ↓ HDAC activity;
HATs↑, ↑ histone acetyltransferase (HAT) activity; ↑ histone H3 & H4
H3↑,
H4↑,
LC3II↑, ↑ LC3-II
c-Raf↓, ↓ c-RAF
SIRT3↑, ↑ Sirt3 mRNA & protein; ↓ Hif-1α protein
Hif1a↓,
ER Stress↑, ↑ ER stress signalling pathway activation; ↑ GRP78,
GRP78/BiP↑,
cl‑CHOP↑, ↑ cleaved caspase-9 & CHOP;
MMP↓, mitochondrial depolarization
PCNA↓, ↓ cyclin B1, cyclin D1, cyclin D2 & PCNA;
Zeb1↓, ↓ ZEB2 Inhibit
NOTCH3↓, ↓ Notch3/Hes1 pathway
CD133↓, ↓ CD133 & Nestin protein
Nestin↓,
ATG5↑, ↑ Atg7 protein activation; ↑ Atg5;
ATG7↑,
survivin↓, ↓ Mcl-1 & survivin protein
ChemoSen↑, honokiol potentiated the apoptotic effect of both doxorubicin and paclitaxel against human liver cancer HepG2 cells.
SOX2↓, Honokiol was shown to downregulate the expression of Oct4, Nanog, and Sox2 which were known to be expressed in osteosarcoma, breast carcinoma and germ cell tumours
OS↑, Lipo-HNK was also shown to prolong survival and induce intra-tumoral apoptosis in vivo.
P-gp↓, Honokiol was shown to downregulate the expression of P-gp at mRNA and protein levels in MCF-7/ADR, a human breast MDR cancer cell line
Half-Life↓, For i.v. administration, it has been found that there was a rapid rate of distribution followed by a slower rate of elimination (elimination half-life t1/2 = 49.22 min and 56.2 min for 5 mg or 10 mg of honokiol, respectively
Half-Life↝, male and female dogs was assessed. The elimination half-life (t1/2 in hours) was found to be 20.13 (female), 9.27 (female), 7.06 (male), 4.70 (male), and 1.89 (male) after administration of doses of 8.8, 19.8, 3.9, 44.4, and 66.7 mg/kg, respectively.
eff↑, Apart from that, epigallocatechin-3-gallate functionalized chitin loaded with honokiol nanoparticles (CE-HK NP), developed by Tang et al. [224], inhibit HepG2
BioAv↓, extensive biotransformation of honokiol may contribute to its low bioavailability.

4640- HT,    The anti-cancer potential of hydroxytyrosol
- Review, Var, NA
selectivity↑, Hydroxytyrosol selectively kills cancer cells with minimal impact on normal cells by activating both intrinsic and extrinsic apoptotic pathways.
MMP↓, Disruption of Mitochondrial Membrane Potential
Cyt‑c↑, HT reduces mitochondrial membrane potential (ΔΨm), leading to the release of cytochrome c into the cytoplasm, activating caspase-9 and caspase-3, and triggering an apoptotic cascade (Cancer Letters, 2021).
Casp9↑,
Casp3↑,
Bcl-2↓, It downregulates anti-apoptotic proteins (Bcl-2, Bcl-xL) and upregulates pro-apoptotic proteins (Bax, Bak), promoting mitochondrial outer membrane permeabilization (MPTP opening) (Molecular Oncology, 2022).
BAX↑,
MPT↑,
Fas↑, Activation of Death Receptor-Mediated Extrinsic Apoptotic Pathway: Fas/FasL Pathway
PI3K↓, Suppression of PI3K/Akt/mTOR Pathway
Akt↓,
mTOR↓,
Mcl-1↓, decreases the expression of anti-apoptotic proteins (Mcl-1, Survivin) (Cancer Research, 2021).
survivin↓,
STAT3↓, Blockade of STAT3 Pathway
EMT↓, Hydroxytyrosol blocks key steps of tumor metastasis by regulating epithelial-mesenchymal transition (EMT), cell adhesion, invasion, and angiogenesis.
TumCI↓,
angioG↓,
E-cadherin↑, Upregulation of E-cadherin and Downregulation of N-cadherin
N-cadherin↓,
Snail↓, Inhibition of Snail/Twist Transcription Factors
Twist↓,
MMPs↓, Inhibition of Matrix Metalloproteinases (MMPs)
MMP2↓, HT downregulates the activity of MMP-2 and MMP-9, reducing extracellular matrix (ECM) degradation and inhibiting tumor cell invasion (Cancer Prevention Research, 2021).
MMP9↓,
VEGF↓, Suppression of VEGF/VEGFR Pathway
VEGFR2↓,
Hif1a↓, Degradation of HIF-1α: It inhibits the stabilization of HIF-1α under hypoxic conditions, reducing transcription of downstream pro-angiogenic genes (Molecular Cancer Therapeutics, 2021).
CSCs↓, Inhibition of Tumor Stem Cell Properties
CD44↓, Downregulation of CD44/ALDH1 Markers
Wnt↓, Inhibition of Wnt/β-catenin Pathway
β-catenin/ZEB1↓,

4687- LT,  QC,    Dietary Flavonoids Luteolin and Quercetin Suppressed Cancer Stem Cell Properties and Metastatic Potential of Isolated Prostate Cancer Cells
- in-vitro, Pca, DU145
CSCs↓, Since luteolin and quercetin were able to target CSC cells and prevent cancer cell invasiveness, may serve as potential anti-angiogenesis and anti-metastasis agents.
EMT↓, Furthermore, reversed epithelial-mesenchymal transition (EMT) to reduce MMP secretion by Lu and Qu exert inhibition of migration and invasion abilities in A431 cells
MMPs↓,
TumCMig↓,
TumCI↓,

3261- Lyco,    Lycopene and Vascular Health
- Review, Stroke, NA
*Inflam↓, main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabolic profile, and reduce arterial stif
*antiOx↑, It is a much more potent antioxidant than alpha-tocopherol (10 × more potent) or beta-carotene (twice as potent)
*AntiAg↑, lycopene, protecting against myocardial infarction and stroke, is its antiplatelet activity
*cardioP↑, favorable effect in patients with subclinical atherosclerosis, metabolic syndrome, hypertension, peripheral vascular disease, stroke and several other cardiovascular disorders
*SOD↑, Lycopene modulates also the production of antioxidant enzymes, such as superoxide dismutase and catalase
*Catalase↑,
*ROS↓, By reducing oxidative stress and reactive oxygen species, lycopene increases the bioavailability of nitric oxide (NO), improves endothelium-dependent vasodilation and reduces protein, lipids, DNA, and mitochondrial damage (
*mtDam↓,
*cardioP↑, Lycopene exerts a cardioprotective effect against atrazine induced cardiac injury due to its anti-inflammatory effect, by blocking the NF-kappa B pathway and NO production
*NF-kB↓,
*NO↓,
*COX2↓, downregulation of cyclooxygenase 2,
*LDL↓, significant reductions in total and LDL cholesterol were revealed only at doses of, at least, 25 mg lycopene/day
*eff↑, It was noticed that lycopene can potentiate the antiplatelet effect of aspirin, which requires low lycopene diet
*ER Stress↓, Lycopene protects the cardiomyocytes by relieving ERS
*BioAv↑, Lycopene is very bioavailable in the presence of oil, especially in monounsaturated oils, other dietary fats and processed tomato products
*eff↑, Lycopene can increase the antioxidant properties of vitamin C, E, polyphenols and beta-carotene in a synergistic way
*MMPs↓, figure 3, secretion of MMPs
*COX2↓,
*RAGE↓,

3275- Lyco,    Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer
- Review, Var, NA
TumCCA↑, lycopene impedes the progress of the cell cycle from the G1 to the S phase, primarily by diminishing the cyclin D and cyclin E levels.
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓, causes a subsequent inactivation of CDK4 and CDK2 through a reduced phosphorylation of Rb
CDK4↓,
P21↑, lycopene elevates CDK inhibitor, p21, and p53 (tumor suppressor) levels
P53↑,
GSK‐3β↓, Finally, GSK3β, p21, p27, Bad, caspase 9, and p53 (via Mdm2) are inactivated
p27↓,
Akt↓, lycopene inhibits AKT (protein kinase B) and mTOR
mTOR↓,
ROS↓, ability of lycopene to minimize ROS formation and mitigate oxidative stress
MMPs↓, lycopene may decrease the activity of metalloproteinases of the matrix and prevent SK-Hep1 cellular adhesion, invasion, and migration
TumCI↓,
TumCMig↓,
NF-kB↓, well-documented that lycopene inhibits NF-kB binding activity
*iNOS↓, They also claimed that the lycopene caused a decline in the LPS-induced protein and mRNA expression of iNOS,
*COX2↓, Lycopene can therefore decrease the gene expression of iNOS and COX-2 as a non-toxic agent via controlling pro-inflammatory genes
lipid-P↓, suppress gastric cancer by multimodal mechanisms of reduction in lipid peroxidation, elevation in the levels of antioxidants, and enhanced GSH
GSH↑,
NRF2↑, Reportedly, lycopene is known to “upregulate” this ARE system via Nrf2 in vitro (HepG2 and MCF-7 cells)

202- MFrot,  MF,    Systematic simulation of tumor cell invasion and migration in response to time-varying rotating magnetic field
- Analysis, Var, MDA-MB-231
TumCG↓, inhibit tumor progression
MMPs↓,
ECM/TCF↓,

1239- PACs,    Cranberry proanthocyanidins inhibit MMP production and activity
- in-vitro, Nor, NA
*MMPs↓,
*MMP1↓, atalytic activity of MMP-1 and MMP-9 was also inhibited
*MMP9↓,
*NF-kB↓,

1660- PBG,    Emerging Adjuvant Therapy for Cancer: Propolis and its Constituents
- Review, Var, NA
MMPs↓, inhibition of matrix metalloproteinases, anti-angiogenesis
angioG↓,
TumMeta↓, prevention of metastasis, cell-cycle arrest
TumCCA↑,
Apoptosis↑,
ChemoSideEff↓, moderation of the chemotherapy-induced deleterious side effects
eff∅, components conferring antitumor potentials have been identified as caffeic acid phenethyl ester, chrysin, artepillin C, nemorosone, galangin, cardanol, etc
HDAC↓, Taiwanese green propolis extract was used to develop an anticancer agent NBM-HD-3, a histone deacetylase inhibitor (HDACis).
PTEN↑, found to increase phosphatase and tensin homolog (PTEN) and protein kinase B (Akt) protein levelssignificantly, while decreasing phospho-PTEN and phospho-Akt levels markedly
p‑PTEN↓,
p‑Akt↓,
Casp3↑, Propolis induced apoptosis and caspase 3 cleavage, increased phosphorylation of extracellular signal regulated kinase 1/2 (ERK1/2), protein kinase B/Akt1 and focal adhesion kinase (FAK).
p‑ERK↑,
p‑FAK↑,
Dose?, When administered orally for 20 weeks at a dose of 100-300 mg/kg, the protective role against the lingual carcinogenesis was observed
Akt↓, treatment reduced the protein abundance of Akt, Akt1, Akt2, Akt3, phospho-Akt Ser473, phospho-Akt Thr 308, GSK3β, FOXO1, FOXO3a, phospho-FOXO1
GSK‐3β↓,
FOXO3↓,
eff↑, Co-treatment with CAPE and 5-fluorouracil exhibited additive anti-proliferation of TW2.6 cells.
IL2↑, Propolis administration stimulated IL-2 and IL-10 production
IL10↑,
NF-kB↓, reduces the expression of growth and transcription factors, including NF-κB.
VEGF↓, CAPE dose-dependently suppresses vascular endothelial growth factor (VEGF) formation by MDA-231 cells,
mtDam↑, Brazilian red propolis significantly reduced the cancer cell viability through the induction of mitochondrial dysfunction, caspase-3 activity and DNA fragmentation.
ER Stress↑, the action was believed to be due to endoplasmic reticulum stress-related signalling induction of CCAAT/enhancer-binding protein homologous protein (CHOP)
AST↓, Rats,(250 mg/kg) thrice a week for 3 weeks
ALAT↓, Rats,(250 mg/kg) thrice a week for 3 weeks
ALP↓, Rats,(250 mg/kg) thrice a week for 3 weeks
COX2↓, Rats,(250 mg/kg) thrice a week for 3 weeks, Expression of COX-2 and NF-kB p65 was significantly lowered
eff↑, co-treatment of cancer cells with 100 ng/mL TRAIL and 50 μg/mL propolis extract increased the percentage of apoptotic cells to about 66% and caused a significant disruption of membrane potential in LNCaP cells (
Bax:Bcl2↑, decreased Bcl-2/Bax ratio

1666- PBG,    Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer
- Review, Var, NA
ChemoSen↑, Ingredients from propolis also ”sensitize“ cancer cells to chemotherapeutic agents
TumCCA↑, cell-cycle arrest and attenuation of cancer cells proliferation
TumCP↓,
Apoptosis↑,
antiOx↓, behave as antioxidants against peroxyl and hydroxyl radicals,
ROS↑, whereas prooxidant activity is observed in the presence of Cu2+.
COX2↑, Propolis, as well as flavonoids derived from propolis, such as galangin, is a potent COX-2 inhibitor
ER(estro)↓, Some flavonoids from propolis, such as galangin, genistein, baicalein, hesperetin, naringenin, and quercetin, suppressed the proliferation of an estrogen receptor (ER)
cycA1/CCNA1↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
CycB/CCNB1↓,
CDK2↓,
P21↑,
p27↑,
hTERT/TERT↓, leukemia cells, propolis successfully reduced hTERT mRNA expression
HDAC↓, by suppressing expressions of cyclin A, cyclin B, and Cdk2 and by stopping proliferation at the G2 phase, by increasing levels of p21 and p27 proteins, and through the inhibition of telomerase reverse transcriptase (hTERT),
ROS⇅, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
Dose?, Mexican propolis, demonstrated both pro- and anti-inflammatory effects, depending on the dose applied
ROS↓, By scavenging free radicals, chelating metal ions (mainly iron and copper), and stimulating endogenous antioxidant defenses, propolis and its flavonoids directly attenuate the generation of ROS
ROS↑, Romanian propolis [99], exhibits prooxidant properties at high concentrations, by mobilizing endogenous copper ions and DNA-associated copper in cells.
DNAdam↑, propolis, i.e., its polyphenolic components, may induce DNA damage in the presence of transition metal ions.
ChemoSen↑, Algerian propolis + doxorubicin decreased cell viability, prevented cell proliferation and cell cycle progression, induced apoptosis by activating caspase-3 and -9 activities, and increased the accumulation of chemotherapeutic drugs in MDA-MB-231 cel
LOX1↓, propolis components inhibited the LOX pathway
lipid-P↓, Croatian propolis improved psoriatic-like skin lesions induced by irritant agents n-hexyl salicylate or di-n-propyl disulfide by decreasing the extent of lipid peroxidation
NO↑, Taken together, propolis may increase the phagocytic index, NO production, and production of IgG antibodies
Igs↑,
NK cell↑, propolis treatment for 3 days increases the cytotoxic activity of NK cells against murine lymphoma.
MMPs↓, extracts of propolis containing artepillin C and CAPE decreased the formation of new vessels and expression of MMPs and VEGF in various cancer cells
VEGF↓,
Hif1a↓, Brazilian green propolis inhibit the expression of the hypoxia-inducible factor-1 (HIF-1) protein and HIF-1 downstream targets such as glucose transporter 1, hexokinase 2, and VEGF-A
GLUT1↓,
HK2↓,
selectivity↑, Portuguese propolis was selectively toxic against malignant cells.
RadioS↑, propolis increased the lifespan of mice that received the radiotherapy with gamma rays
GlucoseCon↓, Portuguese propolis disturbed the glycolytic metabolism of human colorectal cancer cells, as evidenced by a decrease in glucose consumption and lactate production
lactateProd↓,
eff↓, Furthermore, different pesticides or heavy metals can be found in propolis, which can cause unwanted side effects.
*BioAv↓, Due to the low bioavailability and clinical efficacy of propolis and its flavonoids, their biomedical applications remain limited.

1668- PBG,    Propolis: A Detailed Insight of Its Anticancer Molecular Mechanisms
- Review, Var, NA
antiOx↑, Propolis has well-known therapeutic actions including antioxidative, antimicrobial, anti-inflammatory, and anticancer properties.
Inflam↓,
AntiCan↑,
TumCP↓, primarily by inhibiting cancer cell proliferation, inducing apoptosis
Apoptosis↑,
eff↝, Depending on the bee species, geographic location, plant species, and weather conditions, the chemical makeup of propolis fluctuates significantly
MMPs↓, via inhibiting the metastatic protein expression such as MMPs (matrix metalloproteinases)
TNF-α↓, inhibit inflammatory mediators including tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-1/2 (COX ½), lipoxygenase (LOX), prostaglandins (PGs), and interleukin 1- β (IL1-β)
iNOS↓,
COX2↓,
IL1β↑,
*BioAv↓, Despite the low bioavailability of Artepillin C, a compound with a wide variety of physiological activities
BAX↑, Egyptian propolis extract revealed high apoptotic effects through an increase in BAX (pro-apoptotic protein), caspase-3, and cytochrome-c expression levels, and by a reduction in B-cell lymphoma2 (BCL2)
Casp3↑,
Cyt‑c↑,
Bcl-2↓,
eff↑, enhanced the G0/G1 cell cycle arrest induced by methotrexate
selectivity↑, Thailand propolis on normal and cancerous cells carried out by Umthong et al. found significant differences with the propolis showing cytotoxicity against cancerous but not normal cells.
P53↑, significant increases in the levels of p53 in cells treated with propolis extracts.
ROS↑, propolis induced apoptosis in the SW620 human colorectal cancer cell line through mitochondrial dysfunction caused by high production of reactive oxygen species (ROS) and caspase activation
Casp↑,
eff↑, Galangin- and chrysin-induced apoptosis and mitochondrial membrane potential loss in B16-F1 and A375 melanoma cell lines
ERK↓, Galangin- and chrysin-induced apoptosis and mitochondrial membrane potential loss in B16-F1 and A375 melanoma cell lines
Dose∅, propolis extracts at concentrations of 50 μg/mL significantly increased the levels of TRAIL in cervical tumor cell lines
TRAIL↑,
NF-kB↑, p53, NF-κB, and ROS. These molecules were found to be elevated following exposure of the cells to the alcoholic extract of the propolis
ROS↑,
Dose↑, high concentrations, propolis increased the amounts of integrin β4, ROS, and p53
MMP↓, high expression levels of these molecules, in turn, drove a decrease in mitochondrial membrane potential
DNAdam↑, propolis extract induced DNA fragmentation
TumAuto↑, CAPE, were found to induce autophagy in a breast cancer cell line (MDA-MB-231) through upregulating LC3-II and downregulating p62,
LC3II↑,
p62↓,
EGF↓, downregulation of EGF, HIF-1α, and VEGF
Hif1a↓,
VEGF↓,
TLR4↓, downregulating Toll-like receptor 4 (TLR-4), glycogen synthase kinase 3 beta (GSK3 β), and NF-κB signaling pathways
GSK‐3β↓,
NF-kB↓,
Telomerase↓, Propolis was shown to inhibit the telomerase reverse transcriptase activity in leukemia cells.
ChemoSen↑, Propolis has been shown to increase the activity of existing chemotherapeutic agents and inhibit some of their side effects
ChemoSideEff↓,

4922- PEITC,    Phenethyl Isothiocyanate: A comprehensive review of anti-cancer mechanisms
- Review, Var, NA
Risk↓, strong inverse relationship between dietary intake of cruciferous vegetables and the incidence of cancer.
AntiCan↑, Phenethyl isothiocyanate (PEITC) is present as gluconasturtiin in many cruciferous vegetables with remarkable anti-cancer effects.
TumCP↓, PEITC targets multiple proteins to suppress various cancer-promoting mechanisms such as cell proliferation, progression and metastasis
TumMeta↓,
ChemoSen↑, combination of PEITC with conventional anti-cancer agents is also highly effective in improving overall efficacy
*BioAv↑, ITCs are released from glucosinolates by the action of the enzyme myrosinase. The enzyme myrosinase can be activated by cutting or chewing the vegetables, but heating can destroy its activity
*other↝, Although water cress and broccoli are known to be the richest source, PEITC can also be obtained from turnips and radish
*Dose↝, In a study conducted with human volunteers, approximately 2 to 6 mg of PEITC was found to be released by the consumption of one ounce of watercress
Dose↓, significant anti-cancer effects can be achieved at micromolar concentrations of PEITC.
*BioAv↑, PEITC is highly bioavailable after oral administration. A single dose of 10–100 μmol/kg PEITC in rats resulted in bioavailability ranging between 90–114%
*Dose↝, Furthermore, about 928.5±250nM peak plasma concentration of PEITC was achieved in human subjects, after the consumption of 100g watercress.
*Half-Life↝, time to reach peak plasma concentration was observed to be 2.6h±1.1h with a t1/2 4.9±1.1h
*toxicity↝, long term studies are required to establish the safety profile of PEITC, since regular intake of PEITC can cause its accumulation resulting in cumulative effects, which could be toxic.
GSH↓, The conjugation of PEITC with intracellular glutathione and the subsequent removal of the conjugate result in depletion of glutathione and alteration in redox homeostasis leading to oxidative stress
ROS↑, PEITC-mediated generation of reactive oxygen species (ROS) is known to be a general mechanism of action leading to cytotoxic effects, especially specific to cancer cells
CYP1A1↑, PEITC on one hand causes induction of CYP1A1 and CYP1A2; however, it inhibits activity of certain CytP450 enzymes, such as CYP2E1, CYP3A4 and CYP2A3
CYP1A2↑,
P450↓,
CYP2E1↑,
CYP3A4↓,
CYP2A3/CYP2A6↓,
*ROS↓, PEITC treatment caused a significant increase in the activities of ROS detoxifying enzymes such as glutathione peroxidase1, superoxide dismutase 1 and 2. This was also confirmed in human study where subjects were administered watercress, a major sour
*GPx1↑,
*SOD1↑,
*SOD2↑,
Akt↓, PEITC inhibits Akt, a component of Ras signaling to inhibit tumor growth in several cancer types
EGFR↓, PEITC is also known to inhibit EGFR and HER2, which are important growth factors and regulators of Akt in different cancer models
HER2/EBBR2↓,
P53↑, PEITC-mediated activation of another tumor suppressor, p53 was observed in oral squamous cell carcinoma, causing G0/G1 phase arrest in multiple myeloma,
Telomerase↓, PEITC has been shown to inhibit telomerase activity in prostate and cervical cancer cells
selectivity↑, generation of reactive oxygen species (ROS), which also has been shown to be the basis of selectivity of PEITC toward cancer cells leaving normal cells undamaged [
MMP↓, ROS generation by PEITC leads to mitochondrial deregulation and modulation of proteins like Bcl2, BID, BIM and BAX, causing the release of cytochrome c into cytosol leading to apoptosis
Cyt‑c↑,
Apoptosis↑,
DR4↑, induction of death receptors and Fas-mediated apoptosis
Fas↑,
XIAP↓, PEITC-mediated suppression of anti-apoptotic proteins like XIAP and survivin, which are up-regulated in cancer cells
survivin↓,
TumAuto↑, PEITC induces autophagic cell death in cancer cells
Hif1a↓, PEITC directly or indirectly suppresses HIF1α
angioG↓, is possible that PEITC can block angiogenesis by non-hypoxic mechanisms also.
MMPs↓, Various studies with PEITC have shown suppression of invasion through inhibition of matrix metalloproteinases along with anti-metastatic effects caused by suppression of ERK kinase activity and transcriptional activity of NFkB
ERK↓,
NF-kB↓,
EMT↓, PEITC was also known to inhibit processes, such as epithelial to mesenchymal transition (EMT), cell invasion and migration, which are essential pre-requisites for metastasis
TumCI↓,
TumCMig↓,
Glycolysis↓, reduced rates of glycolysis in PEITC-treated cells and depletion of ATP lead to death in prostate cancer cells
ATP↓,
selectivity↑, PEITC (5μM) treatment suppressed glycolysis in the cancer cells, but no changes were observed in normal cells.
*antiOx↑, the antioxidant effect is achieved at very low ITC levels in normal cells as shown in various animal models
Dose↝, At higher concentrations, ITCs may generate ROS by depleting antioxidant levels. PEITC is known to cause ROS generation, which is the major mechanism of toxicity in cancer cells
other↝, There is a continuous leakage of electrons from the electron transport chain (ETC), which is major source of ROS production. PEITC causes generation of endogenous ROS by disrupting mitochondrial respiratory chain
OCR↓, PEITC also inhibits mitochondrial complex III activity and reduces the oxygen consumption rate in prostate cancer cells
GSH↓, PEITC binds to GSH and causes its depletion in cancer cells leading to ROS-induced cell damage
ITGB1↓, PEITC was found to inhibit major integrins, such as ITGB1, ITGA2 and ITGA6 in prostate cancer cells
ITGB6↓,
ChemoSen↑, Using pre-clinical studies, improved outcomes were observed when the conventional agents, such as docetaxel, metformin, vinblastine, doxorubicin and HDAC inhibitors were combined with PEITC

5210- PI,    Piperine is a potent inhibitor of nuclear factor-kappaB (NF-kappaB), c-Fos, CREB, ATF-2 and proinflammatory cytokine gene expression in B16F-10 melanoma cells
- in-vitro, Melanoma, B16-BL6
IL1β↓, IL-1beta, IL-6, TNF-alpha and GM-CSF. Piperine treatment significantly reduced the above proinflammatory cytokines.
TNF-α↓,
MMPs↓, Piperine could inhibit the matrix metalloproteinase production
p65↓, p65, p50, c-Rel subunits of NF-kappaB and other transcription factors such as ATF-2, c-Fos and CREB were inhibited by the treatment of piperine.
p50↓,
NF-kB↓,
ATF2↓,
cFos↓,
CREB↓,

3595- PI,    Black pepper and health claims: a comprehensive treatise
- Review, Var, NA - Review, AD, NA
*antiOx↑, Black pepper (Piper Nigrum L.) is an important healthy food owing to its antioxidant, antimicrobial potential and gastro-protective modules
*ROS↓, The free-radical scavenging activity of black pepper and its active ingredients might be helpful in chemoprevention and controlling progression of tumor growth.
*chemoP↑,
TumCG↓,
*cognitive↑, piperine assist in cognitive brain functioning, boost nutrient's absorption and improve gastrointestinal functionality
*MMPs↓, They postulated that inhibition of interlukon, matrix metalloproteinase, prostaglandin E2, and activator protein 1 are possible routes for their said properties
*PGE2↓,
*AP-1↓,
*5LO↓, Piperine along with some other components can inhibit the expression of enzymes like 5-lipoxygenase and COX-1 that are responsible for leukotriene and prostaglandin biosynthesis.
*COX1↓,
*other↑, It is widely accepted that black pepper is instrumental to prevent and cure gastrointestinal problems. The black pepper enhances the production of hydrochloric acid from stomach thus improving digestion through stimulation of histamine H2 recepto
*other↑, black pepper has diaphoretic (promotes sweating), and diuretic (promotes urination) properties
*other↑, Moreover, it protects intestinal membranes from gastric secretions and ROS damage owing to antioxidant potential.
*SOD↑, black pepper significantly enhanced the activities of antioxidant enzymes, that is, SOD, CAT, GR, and GST.
*Catalase↑,
*GSTs↑,
*GSR↑,
*other↑, black pepper and its active ingredients improve expression of some digestive enzymes along with increase in the secretion of saliva
*Weight↓, piperine intake may decrease body weight
*BioEnh↑, The black pepper and piperine improve the bioavailability of many drugs.
*BioAv↑, Piperine also boosts the bioavailability of important phyto- chemicals contained in other foods, for example, bioactive com- ponents present in curcumin and green tea
*eff↑, The combination of piperine (2.5 mg/kg, i.p., 21 days) with curcumin (20 and 40 mg/kg, i.p., 21 days) showed improved anti-immobility, neurotransmitter enhancing, and monoamine oxidase inhibitory (MAO-A) effects of curcumin
*CYP3A2↓, combination of curcumin and piperine is most likely to inhibit CYP3A, CYP2C9, UGT, and SULT metabolism within the intestinal mucosa (Volak et al., 2008)
*neuroP↑, Neuroprotective Potential of Black Pepper
*BP↓, Piperine (20 mg/kg/day) decreased the blood pressure caused by the blockage of voltage-dependent calcium channels
*other↑, black pepper oil is one of the strongest appetizer; inhalation stimulates the swallowing in post stroke patients with dysphagia.

1236- PTS,    Pterostilbene inhibits the metastasis of TNBC via suppression of β-catenin-mediated epithelial to mesenchymal transition and stemness
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
TumMeta↓,
EMT↓,
E-cadherin↑,
Zeb1↓,
Snail↓,
β-catenin/ZEB1↓,
CD44↓,
MMPs↓,
CSCs↓, data demonstrated that PTE could repress the stemness of MDA-MB-231 cells through inhibiting mammosphere-formation capability, reducing the expression of CSC biomarkers and stemness associated factors.

3927- PTS,    Effects of Pterostilbene on Cardiovascular Health and Disease
- Review, AD, NA - Review, Stroke, NA
*Inflam↓, remarkable anti-inflammatory and antioxidant effects.
*antiOx↑,
*BioAv↑, high bioavailability and low toxicity in many species has contributed to its promising research prospects.
*toxicity↓,
*NADPH↓, Pterostilbene significantly down-regulates nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX),
*ROS↓, which is the key enzyme family that induces the release of reactive oxygen species (ROS)
*Catalase↑, pterostilbene treatment as it increases the expression levels of catalase (CAT), glutathione (GSH), superoxide dismutase (SOD), and other antioxidants in diabetic rats [
*GSH↑,
*SOD↑,
*TNF-α↓, (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-4), matrix metalloproteinases (MMPs), and cyclooxygenase (COX)-2 are all suppressed by pterostilbene treatment.
*IL1β↓,
*IL4↓,
*MMPs↓,
*COX2↓,
*MAPK↝, anti-inflammatory action of pterostilbene has been proved to be associated with modulating mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) pathways
*NF-kB↓,
*IL8↓, pterostilbene can successfully reverse the elevation of related pro-inflammatory cytokines (IL-8, monocyte chemoattractant protein (MCP)-1, and E-selectin)
*MCP1↓,
*E-sel↓,
*lipid-P↓, Pterostilbene has been demonstrated to reduce lipid peroxidation by regulating the expression of Nrf2, exhibiting anti-peroxidation and anti-hyperlipidemic effects
*NRF2↑,
*PPARα↑, Pterostilbene acts as a potent PPAR-α agonist
*LDL↓, pterostilbene could effectively reduce the plasma low-density lipoprotein (LDL) cholesterol levels of hamsters by 29% and increase the plasma high-density lipoprotein (HDL) cholesterol levels by almost 7%
other↓, Ability to Protect against Stroke


Showing Research Papers: 1 to 50 of 77
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 77

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 2,   ATF3↑, 1,   Catalase↓, 1,   CYP1A1↑, 1,   CYP2E1↑, 1,   frataxin↑, 1,   GSH↓, 3,   GSH↑, 1,   GSR↑, 1,   H2O2↑, 1,   HO-1↑, 1,   lipid-P↓, 2,   lipid-P↑, 3,   NQO1↑, 1,   NRF2↓, 1,   NRF2↑, 6,   OXPHOS↝, 1,   ROS↓, 3,   ROS↑, 24,   ROS⇅, 2,   mt-ROS↑, 1,   SIRT3↓, 1,   SIRT3↑, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 3,   CDC2↓, 3,   CDC25↓, 1,   EGF↓, 1,   p‑MEK↓, 1,   mitResp↓, 1,   MMP↓, 10,   MPT↑, 1,   mtDam↑, 1,   OCR↓, 1,   c-Raf↓, 1,   XIAP↓, 3,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 2,   adiP↑, 1,   ALAT↓, 1,   AMPK↑, 3,   AMPK↝, 1,   ATG7↑, 1,   cMyc↓, 4,   CREB↓, 1,   CYP3A4↓, 1,   FASN↓, 1,   GlucoseCon↓, 1,   GlutMet↓, 1,   glyC↓, 1,   Glycolysis↓, 2,   HK2↓, 1,   IR↓, 1,   lactateProd↓, 1,   LDHA↓, 1,   NADPH↓, 2,   NADPH↑, 1,   PCK1↓, 1,   PPARγ↑, 1,  

Cell Death ⓘ

Akt↓, 13,   Akt↑, 1,   p‑Akt↓, 4,   APAF1↑, 1,   Apoptosis↑, 15,   ATF2↓, 1,   Bak↑, 3,   BAX↑, 13,   Bax:Bcl2↑, 3,   Bcl-2↓, 17,   Bcl-2↑, 1,   Bcl-xL↓, 8,   BID↑, 1,   BIM↑, 2,   Casp↑, 4,   Casp1↑, 1,   Casp2↑, 1,   Casp3↑, 16,   cl‑Casp3↑, 2,   Casp7↑, 1,   cl‑Casp7↑, 1,   Casp8↑, 4,   cl‑Casp8↑, 1,   Casp9↑, 9,   cl‑Casp9↑, 3,   cFLIP↓, 3,   Chk2↓, 1,   Chk2↑, 1,   CK2↓, 3,   Cyt‑c↑, 14,   Diablo↑, 1,   DR4↑, 1,   DR4∅, 1,   DR5↑, 6,   FADD↑, 2,   Fas↑, 5,   FasL↑, 2,   HEY1↓, 1,   HGF/c-Met↓, 1,   hTERT/TERT↓, 1,   IAP1↓, 1,   IAP2↓, 1,   cl‑IAP2↑, 1,   iNOS↓, 1,   JNK↑, 3,   p‑JNK↓, 1,   MAPK↓, 6,   MAPK↑, 1,   Mcl-1↓, 5,   Mcl-1↑, 1,   MDM2↓, 1,   Myc↓, 1,   NOXA↑, 1,   p27↓, 1,   p27↑, 2,   p38↑, 2,   p‑p38↓, 1,   PUMA↑, 1,   survivin↓, 7,   Telomerase↓, 7,   TRAIL↑, 2,   TumCD↑, 2,  

Kinase & Signal Transduction ⓘ

EF-1α↓, 1,   HER2/EBBR2↓, 3,   PAK↓, 1,   Sp1/3/4↓, 2,  

Transcription & Epigenetics ⓘ

cJun↑, 1,   H3↓, 1,   H3↑, 2,   p‑H3↓, 1,   ac‑H3↑, 1,   H4↑, 1,   ac‑H4↑, 1,   HATs↓, 1,   HATs↑, 1,   other↓, 1,   other↝, 2,   p‑pRB↓, 1,   tumCV↓, 5,  

Protein Folding & ER Stress ⓘ

CHOP↑, 4,   cl‑CHOP↑, 1,   eIF2α↑, 1,   ER Stress↑, 6,   GRP78/BiP↓, 1,   GRP78/BiP↑, 2,   HSP27↓, 1,   HSP90↓, 2,   HSPs↓, 1,   p‑PERK↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 2,   Beclin-1↑, 1,   BNIP3↑, 1,   LC3II↑, 2,   LC3s↑, 1,   p62↓, 1,   p62↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

ATM↑, 1,   CHK1↓, 1,   CHK1↑, 1,   DNAdam↑, 4,   DNMT1↓, 1,   DNMTs↓, 3,   MGMT↓, 1,   p16↑, 1,   P53↓, 1,   P53↑, 12,   P53↝, 1,   PARP↑, 2,   cl‑PARP↑, 5,   PARP1↑, 1,   PCNA↓, 2,   SIRT6↓, 1,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 2,   CDK2↓, 5,   CDK4↓, 7,   Cyc↓, 1,   cycA1/CCNA1↓, 2,   CycB/CCNB1↓, 2,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 3,   P21?, 1,   P21↑, 7,   p‑RB1↓, 2,   TumCCA?, 1,   TumCCA↑, 21,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 2,   CD24↓, 1,   CD44↓, 2,   cFos↓, 1,   p‑cMET↑, 1,   CSCs↓, 6,   EMT↓, 11,   ERK↓, 7,   p‑ERK↑, 1,   FGF↓, 1,   FOXO3↓, 1,   FOXO3↑, 2,   GSK‐3β↓, 5,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 2,   HDAC↓, 7,   HDAC1↓, 1,   HDAC10↑, 1,   IGF-1↓, 3,   IGFBP1↑, 1,   IGFBP3↑, 1,   mTOR↓, 5,   mTOR↝, 1,   p‑mTOR↓, 1,   mTORC1↓, 2,   mTORC2↓, 1,   Nanog↓, 2,   Nestin↓, 2,   NOTCH↓, 1,   NOTCH1↓, 2,   NOTCH3↓, 1,   OCT4↓, 2,   PI3K↓, 7,   PTEN↑, 3,   p‑PTEN↓, 1,   RAS↓, 1,   RAS↑, 1,   Shh↓, 1,   SHP1↓, 1,   SOX2↓, 1,   STAT1↓, 1,   STAT3↓, 6,   STAT3↑, 2,   p‑STAT3↓, 3,   STAT4↓, 1,   STAT5↓, 1,   TOP1↓, 1,   TumCG↓, 4,   Wnt?, 1,   Wnt↓, 1,   ZFX↓, 1,  

Migration ⓘ

AntiAg↑, 1,   AP-1↓, 3,   ATPase↓, 1,   Ca+2↑, 4,   cal2↑, 1,   CD31↓, 1,   E-cadherin↓, 2,   E-cadherin↑, 5,   ER-α36↓, 1,   FAK↓, 4,   p‑FAK↑, 1,   GLI2↓, 1,   ITGB1↓, 2,   ITGB3↓, 1,   ITGB4↓, 1,   ITGB6↓, 1,   Ki-67↓, 2,   miR-200b↑, 1,   miR-29b↑, 1,   MMP1↓, 1,   MMP13↓, 1,   MMP2↓, 12,   MMP7↓, 1,   MMP9↓, 11,   MMPs↓, 45,   N-cadherin↓, 2,   PDGF↓, 1,   RECK↑, 1,   Rho↓, 1,   Slug↓, 1,   Snail↓, 4,   SOX4↓, 1,   TGF-β↓, 2,   TIMP1↓, 1,   TIMP1↑, 1,   TIMP2↓, 1,   TIMP2↑, 1,   TumCA↓, 1,   TumCI↓, 11,   TumCMig↓, 10,   TumCP↓, 12,   TumMeta↓, 13,   TumMeta↑, 1,   Twist↓, 2,   TXNIP↑, 1,   uPA↓, 5,   Vim↓, 2,   Zeb1↓, 4,   β-catenin/ZEB1↓, 6,   β-catenin/ZEB1↑, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 16,   ATF4↑, 1,   ECM/TCF↓, 1,   EGFR↓, 7,   EPR↑, 1,   HIF-1↓, 1,   Hif1a↓, 12,   LOX1↓, 1,   NO↑, 1,   PDGFR-BB↓, 1,   VEGF↓, 15,   VEGFR2↓, 3,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 2,   P-gp↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 11,   COX2↑, 1,   CXCR4↓, 1,   Igs↑, 1,   IKKα↓, 1,   p‑IKKα↓, 1,   IL1↓, 1,   IL10↑, 1,   IL12↓, 1,   IL18↓, 1,   IL1β↓, 2,   IL1β↑, 1,   IL2↓, 1,   IL2↑, 1,   IL5↓, 1,   IL6↓, 3,   IL8↓, 1,   Imm↑, 1,   Inflam↓, 4,   IκB↑, 2,   p‑IκB↓, 1,   JAK↓, 1,   JAK1↓, 1,   p‑JAK2↓, 1,   NF-kB↓, 23,   NF-kB↑, 1,   NK cell↑, 2,   p50↓, 1,   p65↓, 3,   PD-L1↓, 1,   PGE2↓, 2,   PSA↓, 1,   TLR4↓, 1,   TNF-α↓, 5,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   ER(estro)↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 3,   BioAv∅, 1,   ChemoSen↑, 15,   ChemoSen∅, 1,   CYP1A2↑, 1,   CYP2A3/CYP2A6↓, 1,   Dose?, 3,   Dose↓, 1,   Dose↑, 1,   Dose↝, 3,   Dose∅, 2,   eff↓, 3,   eff↑, 33,   eff↝, 2,   eff∅, 1,   Half-Life↓, 4,   Half-Life↝, 1,   Half-Life∅, 2,   P450↓, 1,   RadioS↑, 3,   selectivity↑, 8,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AR↓, 2,   AST↓, 1,   BMPs↑, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 7,   GutMicro↑, 1,   HER2/EBBR2↓, 3,   hTERT/TERT↓, 1,   IL6↓, 3,   Ki-67↓, 2,   Myc↓, 1,   NOS2↓, 1,   PD-L1↓, 1,   PSA↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   AntiTum↑, 1,   cardioP↑, 1,   chemoP↑, 5,   chemoPv↑, 3,   ChemoSideEff↓, 3,   hepatoP↑, 1,   neuroP↑, 1,   OS↑, 2,   RenoP↑, 2,   Risk↓, 2,   toxicity∅, 1,  
Total Targets: 388

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 13,   Catalase↑, 5,   GPx↑, 2,   GPx1↑, 1,   GSH↑, 2,   GSR↑, 1,   GSTs↑, 1,   HO-1↑, 1,   lipid-P↓, 3,   NRF2↑, 4,   Prx↑, 1,   RNS↓, 1,   ROS↓, 15,   SOD↑, 5,   SOD1↑, 2,   SOD2↑, 3,  

Mitochondria & Bioenergetics ⓘ

mtDam↓, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   CYP3A2↓, 1,   glucose↓, 1,   LDH↓, 1,   LDL↓, 2,   NADPH↓, 2,   PPARα↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Casp3?, 1,   Casp3↓, 1,   iNOS↓, 2,   MAPK↓, 2,   MAPK↝, 1,  

Transcription & Epigenetics ⓘ

other↓, 2,   other↑, 5,   other↝, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,   P53↓, 1,  

Cell Cycle & Senescence ⓘ

E2Fs↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1R↓, 1,   PI3K↓, 1,   RAS↓, 1,   TRPM7↓, 1,  

Migration ⓘ

5LO↓, 2,   AntiAg↑, 1,   AP-1↓, 2,   E-sel↓, 1,   MMP1↓, 1,   MMP2↓, 1,   MMP9↓, 1,   MMPs↓, 5,   PKCδ↓, 1,   p‑Rac1↓, 1,   RAGE↓, 1,   ZO-1↑, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,   PDGFR-BB↓, 1,  

Barriers & Transport ⓘ

BBB↑, 4,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↓, 1,   COX2↓, 8,   IKKα↑, 1,   IL10↓, 1,   IL10↑, 1,   IL1β↓, 3,   IL4↓, 1,   IL6↓, 3,   IL8↓, 2,   Imm↑, 1,   Inflam↓, 12,   Inflam↑, 1,   JAK↓, 1,   MCP1↓, 1,   NF-kB↓, 8,   PGE2↓, 3,   TNF-α↓, 5,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,  

Protein Aggregation ⓘ

BACE↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CYP19↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 8,   BioAv↑, 8,   BioAv↝, 1,   BioEnh↑, 1,   Dose↝, 4,   Dose∅, 1,   eff↑, 5,   Half-Life↝, 2,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 2,   AST↓, 2,   BP↓, 1,   GutMicro↑, 1,   IL6↓, 3,   LDH↓, 1,   RAGE↓, 1,  

Functional Outcomes ⓘ

AntiCan↓, 1,   AntiCan↑, 2,   AntiDiabetic↑, 3,   Bone Healing↑, 1,   cardioP↑, 6,   chemoP↑, 1,   cognitive↑, 2,   hepatoP↓, 1,   hepatoP↑, 2,   memory↑, 1,   motorD↑, 1,   neuroP↑, 9,   Obesity↓, 1,   RenoP↑, 1,   toxicity↓, 5,   toxicity↝, 2,   Weight↓, 1,   Wound Healing↑, 2,  

Infection & Microbiome ⓘ

AntiFungal↑, 1,   AntiViral↑, 1,   Bacteria↓, 2,  
Total Targets: 114

Scientific Paper Hit Count for: MMPs, Matrix metalloproteinases
9 Quercetin
4 EGCG (Epigallocatechin Gallate)
4 Resveratrol
4 Thymoquinone
3 Apigenin (mainly Parsley)
3 Baicalein
3 Curcumin
3 Propolis -bee glue
3 Rosmarinic acid
2 Astaxanthin
2 Biochanin A
2 Betulinic acid
2 Caffeic Acid Phenethyl Ester (CAPE)
2 Coenzyme Q10
2 Honokiol
2 Lycopene
2 Piperine
2 Pterostilbene
2 Silymarin (Milk Thistle) silibinin
2 Vitamin C (Ascorbic Acid)
1 Silver-NanoParticles
1 Alpha-Lipoic-Acid
1 Ashwagandha(Withaferin A)
1 Aloe anthraquinones
1 beta-glucans
1 immunotherapy
1 Berberine
1 Boswellia (frankincense)
1 Carnosic acid
1 Carvacrol
1 diet FMD Fasting Mimicking Diet
1 Fisetin
1 HydroxyTyrosol
1 Luteolin
1 Magnetic Field Rotating
1 Magnetic Fields
1 Proanthocyanidins
1 Phenethyl isothiocyanate
1 Sulforaphane (mainly Broccoli)
1 Shikonin
1 Aflavin-3,3′-digallate
1 Vitamin K2
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:204  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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