CycB/CCNB1 Cancer Research Results

CycB/CCNB1, Cyclin B: Click to Expand ⟱
Source:
Type:
When cyclin B levels are elevated, cells can enter M phase prematurely and strict control over cell division is lost, which is favorable for cancer development.
Cyclin B is a regulatory protein that plays a crucial role in cell cycle progression, particularly in the transition from the G2 phase to mitosis. Its expression levels can significantly impact cancer progression and patient prognosis.
Cyclin B expression is often elevated in various cancers and is generally associated with poor prognosis.
Cyclin B levels:
-Accumulate during S and G2
-Peak at mitotic entry
-Are rapidly destroyed at metaphase–anaphase transition via the APC/C ubiquitin ligase


Scientific Papers found: Click to Expand⟱
251- AL,    Inhibition of allicin in Eca109 and EC9706 cells via G2/M phase arrest and mitochondrial apoptosis pathway
- in-vitro, ESCC, Eca109 - in-vitro, ESCC, EC9706 - in-vivo, NA, NA
Apoptosis↑,
P53↑,
P21↑,
CHK1↑,
CycB/CCNB1↓,
BAX↑,
Casp3↑,
Casp9↑,
Cyt‑c↑, allicin treatment resulted in Cyt c release from the mitochondria to the cytosol.

2660- AL,    Allicin: A review of its important pharmacological activities
- Review, AD, NA - Review, Var, NA - Review, Park, NA - Review, Stroke, NA
*Inflam↓, It showed neuroprotective effects, exhibited anti-inflammatory properties, demonstrated anticancer activity, acted as an antioxidant, provided cardioprotection, exerted antidiabetic effects, and offered hepatoprotection.
AntiCan↑,
*antiOx↑,
*cardioP↑, This vasodilatory effect helps protect against cardiovascular diseases by reducing the risk of hypertension and atherosclerosis.
*hepatoP↑,
*BBB↑, This allows allicin to easily traverse phospholipid bilayers and the blood-brain barrier
*Half-Life↝, biological half-life of allicin is estimated to be approximately one year at 4°C. However, it should be noted that its half-life may differ when it is dissolved in different solvents, such as vegetable oil
*H2S↑, allicin undergoes metabolism in the body, leading to the release of hydrogen sulfide (H2S)
*BP↓, H2S acts as a vasodilator, meaning it relaxes and widens blood vessels, promoting blood flow and reducing blood pressure.
*neuroP↑, It acts as a neuromodulator, regulating synaptic transmission and neuronal excitability.
*cognitive↑, Studies have suggested that H2S may enhance cognitive function and protect against neurodegenerative diseases like Alzheimer's and Parkinson's by promoting neuronal survival and reducing oxidative stress.
*neuroP↑, various research studies suggest that the neuroprotective mechanisms of allicin can be attributed to its antioxidant and anti-inflammatory properties
*ROS↓,
*GutMicro↑, may contribute to the overall health of the gut microbiota.
*LDH↓, Liu et al. found that allicin treatment led to a significant decrease in the release of lactate dehydrogenase (LDH),
*ROS↓, allicin's capacity to lower the production of reactive oxygen species (ROS), decrease lipid peroxidation, and maintain the activities of antioxidant enzymes
*lipid-P↓,
*antiOx↑,
*other↑, allicin was found to enhance the expression of sphingosine kinases 2 (Sphk2), which is considered a neuroprotective mechanism in ischemic stroke
*PI3K↓, allicin downregulated the PI3K/Akt/nuclear factor-kappa B (NF-κB) pathway, inhibiting the overproduction of NO, iNOS, prostaglandin E2, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha induced by interleukin-1 (IL-1)
*Akt↓,
*NF-kB↓,
*NO↓,
*iNOS↓,
*PGE2↓,
*COX2/PTGS2↓,
*IL6↓,
*TNF-α↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
*MPO↓, Furthermore, allicin significantly decreased tumor necrosis factor-alpha (TNF-α) levels and myeloperoxidase (MPO) activity, indicating its neuroprotective effect against brain ischemia via an anti-inflammatory pathway
*eff↑, Allicin, in combination with melatonin, demonstrated a marked reduction in the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), Kelch-like ECH-associated protein 1 (Keap-1), and NF-κB genes in rats with brain damage induced by acryl
*NRF2↑, Allicin treatment decreased oxidative stress by upregulating Nrf2 protein and downregulating Keap-1 expression.
*Keap1↓,
*TBARS↓, It significantly reduced myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) levels,
*creat↓, and decreased blood urea nitrogen (BUN), creatinine, LDH, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) levels.
*LDH↓,
*AST↓,
*ALAT↓,
*MDA↓,
*SOD↑, Allicin also increased the activity of superoxide dismutase (SOD) as well as the levels of glutathione S-transferase (GST) and glutathione (GSH) in the liver, kidneys, and brain
*GSH↑,
*GSTs↑,
*memory↑, Allicin has demonstrated its ability to improve learning and memory deficits caused by lead acetate injury by promoting hippocampal astrocyte differentiation.
chemoP↑, Allicin safeguards mitochondria from damage, prevents the release of cytochrome c, and decreases the expression of pro-apoptotic factors (Bax, cleaved caspase-9, cleaved caspase-3, and p53) typically activated by cisplatin
IL8↓, Allicin has been found to regulate the immune system and reduce the levels of TNF-α and IL-8.
Cyt‑c↑, In addition, allicin was reported to induce cytochrome c, increase expression of caspase 3 [86], caspase 8, 9 [82,87], caspase 12 [80] along with enhanced p38 protein expression levels [81], Fas expression levels [82].
Casp3↑,
Casp8↑,
Casp9↑,
Casp12↑,
p38↑,
Fas↑,
P53↑, Also, significantly increased p53, p21, and CHK1 expression levels decreased cyclin B after allicin treatment.
P21↑,
CHK1↓,
CycB/CCNB1↓,
GSH↓, Depletion of GSH and alterations in intracellular redox status have been found to trigger activation of the mitochondrial apoptotic pathway was the antiproliferative function of allicin
ROS↑, Hepatocellular carcinoma (HCC) cells were sensitised by allicin to the mitochondrial ROS-mediated apoptosis induced by 5-fluorouracil
TumCCA↑, According to research findings, allicin has been shown to decrease the percentage of cells in the G0/G1 and S phases [87], while causing cell cycle arrest at the G2/M phase
Hif1a↓, Allicin treatment was found to effectively reduce HIF-1α protein levels, leading to decreased expression of Bcl-2 and VEGF, and suppressing the colony formation capacity and cell migration rate of cancer cells
Bcl-2↓,
VEGF↓,
TumCMig↓,
STAT3↓, antitumor properties of allicin have been attributed to various mechanisms, including promotion of apoptosis, inhibition of STAT3 signaling
VEGFR2/KDR/Flk1↓, suppression of VEGFR2 and FAK phosphorylation
p‑FAK↓,

7400- Amla,    Amla (Emblica officinalis Gaertn), a wonder berry in the treatment and prevention of cancer
- Review, Var, NA
radioP↑, Amla is also reported to possess radiomodulatory, chemomodulatory, chemopreventive effects, free radical scavenging, antioxidant, anti-inflammatory, antimutagenic and immunomodulatory activities,
ChemoSen↑, Together these observations suggest that it is quite possible that amla prevents doxorubicin-induced cardiotoxicity to the normal cardiac myoblasts and, concomitantly, sensitizes the antineoplastic effects on cancer cells.
chemoPv↑,
*ROS↓,
antiOx↑,
Inflam↓,
Imm↑, Studies have shown that amla enhances natural killer (NK) cell activity and antibody-dependent cellular cytotoxicity in BALB/c mice bearing Dalton’s lymphoma ascites tumor.
*hepatoP↑, Amla is also reported to possess hepatoprotective, cardioprotective, diuretic, laxative, refrigerant, stomachic, restorative, alterative, antipyretic, anti-inflammatory properties
*cardioP↑,
*lipid-P↓, Amla decreases lipid peroxidation
TumCCA↑, It also induces G2/M phase cell cycle arrest by regulating 14-3-3b release from Cdc25C; activation of chk2; decreasing CDK1, cyclin B1, and Cdc25C;
Chk2↑,
CDK1↓,
CycB/CCNB1↓,
CDC25↓,
TumMeta↓, Amla and some of its constituents prevent metastasis

1353- And,    Andrographolide Induces Apoptosis and Cell Cycle Arrest through Inhibition of Aberrant Hedgehog Signaling Pathway in Colon Cancer Cells
- in-vitro, Colon, HCT116
ChemoSen↑, combination with 5FU, andrographolide exhibited synergistic effect
TumCCA↑, G2/M phase arrest
CDK1↓,
CycB/CCNB1↓,
HH↓, repressed the colon cancer cell growth via inhibiting Hh signaling pathway
Smo↓,
Gli1↓,

177- Api,    Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression
- in-vitro, BC, MDA-MB-231
Cyc↓, Cyclin A
CycB/CCNB1↓,
CDK1↓,
P21↑,
PCNA↝,
HDAC↓, apigenin treatment for 48 h suppressed HDAC activity in MDA-MB-231 cells in a dose-dependent manner
TumCP↓, Apigenin Inhibited MDA-MB-231 Cell Proliferation
TumCCA↑, Apigenin Induced G2/M Arrest in MDA-MB-231 Cells
ac‑H3↑, H3 acetylation increased in time-dependent
TumW↓, apigenin treatment significantly reduced the tumor volume and tumor weight
TumVol↓,

173- Api,    Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells
- in-vitro, Colon, HCT116
CycB/CCNB1↓,
cDC2↓,
CDC25↓,
P53↑,
P21↑,
cl‑PARP↑, cleavage
proCasp8↓, Apigenin induced poly (ADP-ribose) polymerase (PARP) cleavage and decreased the levels of procaspase-8, -9 and -3
proCasp9↓,
proCasp3↓,

1545- Api,    The Potential Role of Apigenin in Cancer Prevention and Treatment
- Review, NA, NA
TNF-α↓, Apigenin downregulates the TNFα
IL6↓,
IL1α↓,
P53↑,
Bcl-xL↓,
Bcl-2↓,
BAX↑,
Hif1a↓, Apigenin inhibited HIF-1alpha and vascular endothelial growth factor expression
VEGF↓,
TumCCA↑, Apigenin exposure induces G2/M phase cell cycle arrest, DNA damage, apoptosis and p53 accumulation
DNAdam↑,
Apoptosis↑,
CycB/CCNB1↓,
cycA1/CCNA1↓,
CDK1↓,
PI3K↓,
Akt↓,
mTOR↓,
IKKα↓, , decreases IKKα kinase activity,
ERK↓,
p‑Akt↓,
p‑P70S6K↓,
p‑S6↓,
p‑ERK↓, decreased the expression of phosphorylated (p)-ERK1/2 proteins, p-AKT and p-mTOR
p‑P90RSK↑,
STAT3↓,
MMP2↓, Apigenin down-regulated Signal transducer and activator of transcription 3target genes MMP-2, MMP-9 and vascular endothelial growth factor
MMP9↓,
TumCP↓, Apigenin significantly suppressed colorectal cancer cell proliferation, migration, invasion and organoid growth through inhibiting the Wnt/β-catenin signaling
TumCMig↓,
TumCI↓,
Wnt/(β-catenin)↓,

3391- ART/DHA,    Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug
- Review, Var, NA
TumCP↓, inhibiting cancer proliferation, metastasis, and angiogenesis.
TumMeta↓,
angioG↓,
TumVol↓, reduces tumor volume and progression
BioAv↓, artemisinin has low solubility in water or oil, poor bioavailability, and a short half-life in vivo (~2.5 h)
Half-Life↓,
BioAv↑, semisynthetic derivatives of artemisinin such as artesunate, arteeter, artemether, and artemisone have been effectively used as antimalarials with good clinical efficacy and tolerability
eff↑, preloading of cancer cells with iron or iron-saturated holotransferrin (diferric transferrin) triggers artemisinin cytotoxicity
eff↓, Similarly, treatment with desferroxamine (DFO), an iron chelator, renders compounds inactive
ROS↑, ROS generation may contribute with the selective action of artemisinin on cancer cells.
selectivity↑, Tumor cells have enhanced vulnerability to ROS damage as they exhibit lower expression of antioxidant enzymes such as superoxide dismutase, catalase, and gluthatione peroxidase compared to that of normal cells
TumCCA↑, G2/M, decreased survivin
survivin↓,
BAX↑, Increased Bax, activation of caspase 3,8,9 Decreased Bc12, Cdc25B, cyclin B1, NF-κB
Casp3↓,
Casp8↑,
Casp9↑,
CDC25↓,
CycB/CCNB1↓,
NF-kB↓,
cycD1/CCND1↓, decreased cyclin D, E, CDK2-4, E2F1 Increased Cip 1/p21, Kip 1/p27
cycE/CCNE↓,
E2Fs↓,
P21↑,
p27/CDKN1B↑,
ADP:ATP↑, Increased poly ADP-ribose polymerase Decreased MDM2
MDM2↓,
VEGF↓, Decreased VEGF
IL8↓, Decreased NF-κB DNA binding [74, 76] IL-8, COX2, MMP9
COX2/PTGS2↓,
MMP9↓,
ER Stress↓, ER stress, degradation of c-MYC
cMyc↓,
GRP78/BiP↑, Increased GRP78
DNAdam↑, DNA damage
AP-1↓, Decreased NF-κB, AP-1, Decreased activation of MMP2, MMP9, Decreased PKC α/Raf/ERK and JNK
MMP2↓,
PKCδ↓,
Raf↓,
ERK↓,
JNK↓,
PCNA↓, G2, decreased PCNA, cyclin B1, D1, E1 [82] CDK2-4, E2F1, DNA-PK, DNA-topo1, JNK VEGF
CDK2↓,
CDK4↓,
TOP2↓, Inhibition of topoisomerase II a
uPA↓, Decreased MMP2, transactivation of AP-1 [56, 88] NF-κB uPA promoter [88] MMP7
MMP7↓,
TIMP2↑, Increased TIMP2, Cdc42, E cadherin
Cdc42↑,
E-cadherin↑,

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/DDIT3↑,
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/PTGS2↓,
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↓,

4823- ASTX,    Astaxanthin increases radiosensitivity in esophageal squamous cell carcinoma through inducing apoptosis and G2/M arrest
- in-vitro, ESCC, NA
RadioS↑, It was shown that ATX improved radiosensitivity of ESCC cells and induced apoptosis and G2/M arrest via inhibiting Bcl2, CyclinB1, Cdc2, and promoting Bax expression.
Apoptosis↑,
TumCCA↑,
Bcl-2↓,
CycB/CCNB1↓,
CDC2↓,
BAX↑,

5362- AV,    Anti-cancer effects of aloe-emodin: a systematic review
- Review, Var, NA
AntiCan↑, Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule.
eff↝, The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type.
TumCP↓, most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death;
TumCMig↓,
TumCI↓,
TumCCA↑,
TumCD↑,
MMP↓, mitochondrial membrane and redox perturbations; and modulation of immune signaling.
ROS↑, which coincide with deleterious effects on mitochondrial membrane permea-bility and/or oxidative stress via exacerbated ROS production.
Apoptosis↑, In bladder cancer cells (T24), aloe-emodin induced time-and dose-dependent apoptosis [7]
CDK1↓, reduced levels of cyclin-dependent kinase (CDK) 1, cyclin B1, and BCL-2 after treatment with aloe-emodin.
CycB/CCNB1↓,
Bcl-2↓,
PCNA↓, Increases in cyclin B1, CDK1, and alkaline phosphatase (ALP) activity were observed along with inhibition of proliferating cell nuclear antigen (PCNA), showing decreased proliferation.
ATP↓, human lung non-small cell car¬cinoma (H460). They found a time- de¬pendent reduction in ATP, lower ATP synthase expression
ER Stress↑, hypothesized to cause apoptosis by augmenting endoplasmic reticulum stress [16].
cl‑Casp3↑, (HepG2) cells underwent apoptosis through a cas-pase-dependent pathway with cleavage and activation of caspases-3/9 and cleavage of PARP [24]
cl‑Casp9↑,
cl‑PARP↑,
MMP2↓, Matrix metalloproteinase-2 was significantly decreased, with an increase in ROS and cytosolic calcium.
Ca+2↑,
DNAdam↑, U87 malignant glioma cells through disruption of mitochondrial membrane potential, cell cycle arrest in the S phase, and DNA fragmentation in a time-dependent manner with minimal necrosis
Akt↓, Prostate cancer. Following treatment with aloe-emodin, mTORC2's down¬stream enzymes, AKT and PKCa, were inhibited
PKCδ↓,
mTORC2↓, Proliferation of PC3 cells was inhibited as a result of aloe-emodin binding to mTORC2, with inhibition of mTORC2 kinase activity.
GSH↓, Skin cancer. Intracellular ROS increased, while intra-cellular-reduced glutathione (GSH) was depleted and BCL-2 (anti-apoptotic protein) was down-regulated.
ChemoSen↑, Aloe-emodin also sensitizes skin cancer cells to chemo-therapy. aloe-emodin and emodin potentiated the therapeutic effects of cisplatin, doxo-rubicin, 5-fluorouracil

5498- Ba,    Inhibition of 12-lipoxygenase during baicalein-induced human lung nonsmall carcinoma H460 cell apoptosis
- in-vitro, Lung, H460
12LOX↓, Baicalein is known as a 12-lipoxygenase (12-LOX) inhibitor.
Dose↝, exposure to 50muM baicalein, cell cycle analysis revealed an increase in the cell population in S-phase.
TumCCA↑,
CDK1↓, baicalein decreased the protein levels of cdk1 and cyclin B1, which are the regulating proteins of S-phase transition to G2/M-phase, in this study.
CycB/CCNB1↓,
Apoptosis↑, baicalein induced the most of H460 cell apoptosis after treatment for 48h
Bcl-2↓, accompanied by decreasing in Bcl-2 and proform of caspase-3 and increasing p53 and Bax protein levels.
P53↑,
BAX↑,
TumCP↓, baicalein, a 12-LOX inhibitor, inhibits the proliferation of H460 cells via S-phase arrest and induces apoptosis in association with the regulation of molecules in the cell cycle and apoptosis-related proteins.

2290- Ba,    Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer
- Review, GI, NA
p‑mTOR↓, Baicalein treatment decreased the expression levels of p-mTOR, p-Akt, p-IκB and NF-κB proteins, and suppressed GC cells by inhibiting the PI3K/Akt
p‑Akt↓,
p‑IKKα↓,
NF-kB↓,
PI3K↓,
Akt↓,
ROCK1↓, Baicalin reduces HCC proliferation and metastasis by inhibiting the ROCK1/GSK-3β/β-catenin signaling pathway
GSK‐3β↓,
CycB/CCNB1↓, Baicalein induces S-phase arrest in gallbladder cancer cells by down-regulating Cyclin B1 and Cyclin D1 in gallbladder cancer BGC-SD and SGC996 cells while up-regulating Cyclin A
cycD1/CCND1↓,
cycA1/CCNA1↑,
CDK4↓, Following baicalein treatment, there is a down-regulation of Ezrin, CyclinD1, and CDK4, as well as an up-regulation of p53 and p21 protein levels, thereby leading to the induction of CRC HCT116 cell cycle arrest
P53↑,
P21↑,
TumCCA↑,
MMP2↓, baicalein was able to inhibit the metastasis of gallbladder cancer cells by down-regulating ZFX, MMP-2 and MMP-9.
MMP9↓,
EMT↓, Baicalein treatment effectively inhibits the snail-induced EMT process in CRC HT29 and DLD1 cells
Hif1a↓, Baicalein inhibits VEGF by downregulating HIF-1α, a crucial regulator of angiogenesis
Shh↓, baicalein inhibits the metastasis of PC by impeding the Shh pathway
PD-L1↓, Baicalin and baicalein down-regulate PD-L1 expression induced by IFN-γ by reducing STAT3 activity
STAT3↓,
IL1β↓, baicalein therapy significantly diminishes the levels of pro-inflammatory cytokines such as interleukin-1 beta (IL-1β), IL-2, IL-6, and GM-CSF
IL2↓,
IL6↓,
PKM2↓, Baicalein, by reducing the expression levels of HIF-1A and PKM2, can inhibit the glycolysis process in ESCC cells
HDAC10↓, Baicalein treatment increases the level of miR-3178 and decreases HDAC10 expression, resulting in the inactivation of the AKT signaling pathways.
P-gp/ABCB1↓, baicalein reverses P-glycoprotein (P-gp)-mediated resistance in multidrug-resistant HCC (Bel7402/5-FU) cells by reducing the levels of P-gp and Bcl-xl
Bcl-xL↓,
eff↓, Baicalein combined with gemcitabine/docetaxel promotes apoptosis of PC cells by activating the caspase-3/PARP signaling pathway
BioAv↓, baicalein suffers from low water solubility and susceptibility to degradation by the digestive system
BioAv↑, Encapsulation of baicalein into liposomal bilayers exhibits a therapeutic efficacy close to 90% for PDAC

2674- BBR,    Berberine: A novel therapeutic strategy for cancer
- Review, Var, NA - Review, IBD, NA
Inflam↓, anti-inflammatory, antidiabetic, antibacterial, antiparasitic, antidiarrheal, antihypertensive, hypolipidemic, and fungicide.
AntiCan↑, elaborated on the anticancer effects of BBR through the regulation of different molecular pathways such as: inducing apoptosis, autophagy, arresting cell cycle, and inhibiting metastasis and invasion.
Apoptosis↑,
TumAuto↑,
TumCCA↑,
TumMeta↓,
TumCI↓,
eff↑, BBR is shown to have beneficial effects on cancer immunotherapy.
eff↑, BBR inhibited the release of Interleukin 1 beta (IL-1β), Interferon gamma (IFN-γ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-alpha (TNF-α) from LPS stimulated lymphocytes by acting as a dopamine receptor antagonist
CD4+↓, BBR inhibited the proliferation of CD4+ T cells and down-regulated TNF-α and IL-1 and thus, improved autoimmune neuropathy.
TNF-α↓,
IL1↓,
BioAv↓, On the other hand, P-Glycoprotein (P-gp), a secretive pump located in the epithelial cell membrane, restricts the oral bioavailability of a variety of medications, such as BBR. The use of P-gp inhibitors is a common and effective way to prevent this
BioAv↓, Regardless of its low bioavailability, BBR has shown great therapeutic efficacy in the treatment of a number of diseases.
other↓, BBR has been also used as an effective therapeutic agent for Inflammatory Bowel Disease (IBD) for several years
AMPK↑, inhibitory effects on inflammation by regulating different mechanisms such as 5′ Adenosine Monophosphate-Activated Protein Kinase (AMPK. Increase of AMPK
MAPK↓, Mitogen-Activated Protein Kinase (MAPK), and NF-κB signaling pathways
NF-kB↓,
IL6↓, inhibiting the expression of proinflammatory genes such as IL-1, IL-6, Monocyte Chemoattractant Protein 1 (MCP1), TNF-α, Prostaglandin E2 (PGE2), and Cyclooxygenase-2 (COX-2)
MCP1/CCL2↓,
PGE2↓,
COX2/PTGS2↓,
*ROS↓, BBR protected PC-12 cells (normal) from oxidative damage by suppressing ROS through PI3K/AKT/mTOR signaling pathways
*antiOx↑, BBR therapy improved the antioxidant function of mice intestinal tissue by enhancing the levels of glutathione peroxidase and catalase enzymes.
*GPx↑,
*Catalase↑,
AntiTum↑, Besides, BBR leaves great antitumor effects on multiple types of cancer such as breast cancer,69 bladder cancer,70 hepatocarcinoma,71 and colon cancer.72
TumCP↓, BBR exerts its antitumor activity by inhibiting proliferation, inducing apoptosis and autophagy, and suppressing angiogenesis and metastasis
angioG↓,
Fas↑, by increasing the amounts of Fas receptor (death receptor)/FasL (Fas ligand), ROS, ATM, p53, Retinoblastoma protein (Rb), caspase-9,8,3, TNF-α, Bcl2-associated X protein (Bax), BID
FasL↑,
ROS↑,
ATM↑,
P53↑,
RB1↑,
Casp9↑,
Casp8↑,
Casp3↓,
BAX↑,
Bcl-2↓, and declining Bcl2, Bcl-X, c-IAP1 (inhibitor of apoptosis protein), X-linked inhibitor of apoptosis protein (XIAP), and Survivin levels
Bcl-xL↓,
IAP1↓,
XIAP↓,
survivin↓,
MMP2↓, Furthermore, BBR suppressed Matrix Metalloproteinase-2 (MMP-2), and MMP-9 expression.
MMP9↓,
CycB/CCNB1↓, Inhibition of cyclin B1, cdc2, cdc25c
CDC25↓,
CDC25↓,
Cyt‑c↑, BBR inhibited tumor cell proliferation and migration and induced mitochondria-mediated apoptosis pathway in Triple Negative Breast Cancer (TNBC) by: stimulating cytochrome c release from mitochondria to cytosol
MMP↓, decreased the mitochondrial membrane potential, and enabled cytochrome c release from mitochondria to cytosol
RenoP↑, BBR significantly reduced the destructive effects of cisplatin on the kidney by inhibiting autophagy, and exerted nephroprotective effects.
mTOR↓, U87 cell, Inhibition of m-TOR signaling
MDM2↓, Downregulation of MDM2
LC3II↑, Increase of LC3-II and beclin-1
ERK↓, BBR stimulated AMPK signaling, resulting in reduced extracellular signal–regulated kinase (ERK) activity and COX-2 expression in B16F-10 lung melanoma cells
COX2/PTGS2↓,
MMP3↓, reducing MMP-3 in SGC7901 GC and AGS cells
TGF-β↓, BBR suppressed the invasion and migration of prostate cancer PC-3 cells by inhibiting TGF-β-related signaling molecules which induced Epithelial-Mesenchymal Transition (EMT) such as Bone morphogenetic protein 7 (BMP7),
EMT↑,
ROCK1↓, inhibiting metastasis-associated proteins such as ROCK1, FAK, Ras Homolog Family Member A (RhoA), NF-κB and u-PA, leading to in vitro inhibition of MMP-1 and MMP-13.
FAK↓,
RAS↓,
Rho↓,
NF-kB↓,
uPA↓,
MMP1↓,
MMP13↓,
ChemoSen↑, recent studies have indicated that it can be used in combination with chemotherapy agents

5639- BCA,    Biochanin A Induces Apoptosis in MCF-7 Breast Cancer Cells through Mitochondrial Pathway and Pi3K/AKT Inhibition
- in-vitro, BC, NA
TumCP↓, Biochanin A inhibited cell proliferation, increased reactive oxygen species formation, and induced apoptosis.
ROS↑,
Apoptosis↑,
Bcl-2↓, Biochanin A-treated cells exhibited lower expression of the Bcl-2, p-PI3K and p-AKT and higher expression of proapoptotic genes, including Bax, Caspase-3, Caspase-9, and cytochrome c.
p‑PI3K↓,
p‑Akt↓,
BAX↑,
Casp3↑,
Casp9↑,
Cyt‑c↑,
CycD3↓, gene expression levels of cyclin D3, cyclin B1, CDK1, CDK2, and CDK4 were downregulated
CycB/CCNB1↓,
CDK1↓,
CDK2↓,
CDK4↓,
P21↑, while the expression levels of p21, p27, and p53 were significantly upregulated
p27/CDKN1B↑,
P53↑,
tumCV↓, These results suggest that Biochanin A can suppress the viability of breast cancer cells and induce apoptosis via the mitochondrial pathway
PI3K↓, inhibition of the Pi3K/Akt signaling pathway and modulation of cell cycle markers.
Akt↓,

2718- BetA,    The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis
- in-vitro, AML, U937
TumCCA↑, BA exerted a significant cytotoxic effect on U937 cells through blocking cell cycle arrest at the G2/M phase and inducing apoptosis, and that the intracellular reactive oxygen species (ROS) levels increased after treatment with BA.
Apoptosis↑,
i-ROS↑,
cycA1/CCNA1↓, down-regulation of cyclin A and cyclin B1, and up-regulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1 revealed the G2/M phase arrest mechanism of BA.
CycB/CCNB1↓,
P21↑,
Cyt‑c↑, BA induced the cytosolic release of cytochrome c by reducing the mitochondrial membrane potential with an increasing Bax/Bcl-2 expression ratio.
MMP↓,
Bax:Bcl2↑,
Casp9↑, BA also increased the activity of caspase-9 and -3, and subsequent degradation of the poly (ADP-ribose) polymerase.
Casp3↑,
PARP↓,
eff↓, However, quenching of ROS by N-acetyl-cysteine, an ROS scavenger, markedly abolished BA-induced G2/M arrest and apoptosis, indicating that the generation of ROS plays a key role in inhibiting the proliferation of U937 cells by BA treatment.
*antiOx↑, Accumulated evidence demonstrates that BA possesses various biological activities, including antioxidant, anti-inflammatory, hepatoprotective, and anti-tumor effects
*Inflam↓,
*hepatoP↑,
selectivity↑, BA are complex and depends on the type of cancer cells, without causing toxicity toward normal cells
NF-kB↓, Shen et al. (2019) recently reported that the suppression of the nuclear factor-kappa B pathway increased downstream oxidant effectors, thereby promoting the generation of reactive oxygen species (ROS) in BA-stimulated multiple myeloma cells.
*ROS↓, Although BA is known to have antioxidant activity that blocks the accumulation of ROS due to oxidative stress in normal cells (Cheng et al. 2019;

2719- BetA,    Betulinic Acid Restricts Human Bladder Cancer Cell Proliferation In Vitro by Inducing Caspase-Dependent Cell Death and Cell Cycle Arrest, and Decreasing Metastatic Potential
- in-vitro, CRC, T24/HTB-9 - in-vitro, Bladder, UMUC3 - in-vitro, Bladder, 5637
TumCD↑, BA induced cell death in bladder cancer cells and that are accompanied by apoptosis, necrosis, and cell cycle arrest.
Apoptosis↑,
TumCCA↑,
CycB/CCNB1↓, BA decreased the expression of cell cycle regulators, such as cyclin B1, cyclin A, cyclin-dependent kinase (Cdk) 2, cell division cycle (Cdc) 2, and Cdc25c
cycA1/CCNA1↓,
CDK2↓,
CDC25↓,
mtDam↑, BA-induced apoptosis was associated with mitochondrial dysfunction that is caused by loss of mitochondrial membrane potential, which led to the activation of mitochondrial-mediated intrinsic pathway.
BAX↑, BA up-regulated the expression of Bcl-2-accociated X protein (Bax) and cleaved poly-ADP ribose polymerase (PARP), and subsequently activated caspase-3, -8, and -9.
cl‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Snail↓, decreased the expression of Snail and Slug in T24 and 5637 cells, and matrix metalloproteinase (MMP)-9 in UMUC-3 cells.
Slug↓,
MMP9↓,
selectivity↑, Among the bladder cancer cell lines, 5637 cells were much more sensitive to BA than T24 or UMUC-3 cells under the same conditions. However, BA does not affect cell growth in normal cell lines including RAW 264.7
MMP↓, BA Induces Loss of Mitochondrial Membrane Potential (MMP, ΔΨm) in Human Bladder Cancer Cells
ROS∅, As a result, we found that BA did not affect intracellular ROS levels in all three bladder cancer cells. In addition, BA-induced cell viability inhibition was not restored by NAC pre-treatment
TumCMig↓, BA Decreases Migration and Invasion of Human Bladder Cancer Cells
TumCI↓,

5720- BF,    Acetyl-bufalin shows potent efficacy against non-small-cell lung cancer by targeting the CDK9/STAT3 signalling pathway
- in-vitro, NSCLC, NA
STAT3↓, acetyl-bufalin impaired the complex formation of CDK9 and STAT3, decreased the expressions of P-STAT3, and transcribed target genes such as cyclin B1, CDC2, MCL-1, Survivin, VEGF, BCL2
CycB/CCNB1↓,
CDC2↓,
Mcl-1↓,
survivin↓,
VEGF↓,
Bcl-2↓,
BAX↑, and it upregulated the expression levels of BAX and caspase-3 activity.
Casp3↑,

2781- CHr,  PBG,    Chrysin a promising anticancer agent: recent perspectives
- Review, Var, NA
PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2/PTGS2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

1145- CHr,    Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways
- in-vitro, Cerv, HeLa
tumCV↓,
BAX↑,
BID↑,
BOK↑,
APAF1↑,
TNF-α↑,
FasL↑,
Fas↑,
FADD↑,
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
Mcl-1↓,
NAIP↓,
Bcl-2↓,
CDK4↓,
CycB/CCNB1↓,
cycD1/CCND1↓,
cycE1↓,
TRAIL↑,
p‑Akt↓,
Akt↓,
mTOR↓,
PDK1↓,
BAD↓,
GSK‐3β↑,
AMPK↑, AMPKa
p27/CDKN1B↑,
P53↑,

6162- Cin,    Anticancer Potential and Molecular Mechanisms of Cinnamaldehyde and Its Congeners Present in the Cinnamon Plant
- Review, Var, NA
AntiCan↑, Cinnamaldehyde and its congeners have shown their ability to act against several cancers.
Apoptosis↑, graphical abstract
ROS↑,
BAX↑,
Cyt‑c↑,
Fas↑,
Casp9↑,
E-cadherin↑,
Casp7↑,
PARP↑,
Bak↑,
AMPK↑,
Ca+2↑,
BAD↑,
MMP↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,
ERK↓,
VEGF↓,
TumCP↓,
MAPK↓,
mTOR↓,
PI3K↓,
PCNA↓,
Bcl-2↓,
TumCCA↑, Some of the mechanistic approaches include the induction of apoptosis, cell cycle arrest, interruption in angiogenesis, free radical scavenging, inhibition of inflammation, and interference with cellular invasion and metastasis.
angioG↓,
*ROS↓,
Inflam↓,

6334- Cro,  Eug,  Rad,    Crocin and eugenol enhance radiosensitivity in oral squamous cell carcinoma cells via apoptotic pathways and cell cycle regulation. Type of study: in vitro
- in-vitro, OS, NA
tumCV↓, Both crocin and eugenol independently decreased OSCC cell viability and triggered apoptosis in a dose-dependent way.
RadioS↑, When used with IR, they worked together to boost cytotoxicity at moderate doses (CI < 1).
TumCCA↑, Crocin caused early G1 arrest followed by G2/M accumulation, while eugenol strongly induced G2/M arrest and increased sub-G1 fractions.
BAX↑, activation of the intrinsic apoptotic pathway (↑Bax, ↑Caspase-3, ↓Bcl-2) and reduced levels of Cyclin A/B transcripts.
Casp3↑,
Bcl-2↓,
cycA1/CCNA1↓,
CycB/CCNB1↓,

6189- Cuc,    Cucurbitacin B inhibits proliferation and induces apoptosis via STAT3 pathway inhibition in A549 lung cancer cells
- in-vitro, Lung, A549
TumCP↓, (CuB), one of the most potent and widely used cucurbitacins, inhibits proliferation and induces apoptosis in the A549 lung cancer cell line.
Apoptosis↑,
TumCCA↑, , with cell cycle inhibition and cyclin B1 downregulation.
CycB/CCNB1↓,
Cyt‑c↑, associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition.
STAT3↓,
Casp3↑, CuB induces caspase-3 and -9 activation
Casp9↑,
MMP↓, The results indicated that cucurbitacin B treatment induced significant disruption of the Δψm.

6190- Cuc,    Cucurbitacin B induces G2 arrest and apoptosis via a reactive oxygen species-dependent mechanism in human colon adenocarcinoma SW480 cells
- in-vitro, Colon, SW480
ROS↑, Here, we demonstrate for the first time that cucB inhibited growth of human colon cancer SW480 cells through a reactive oxygen species (ROS)-dependent mechanism.
TumCCA↑, CucB induced G(2) phase arrest and apoptosis in a dose-dependent manner.
Apoptosis↑,
CycB/CCNB1↓, cucB reduced the expression of cyclin B1 and cdc25C proteins and activated caspases in SW480 cells
CDC25↓,
Casp↓,
eff↓, N-acetylcysteine(NAC), a well-known antioxidant, reduced the changes in expression of the molecules, and suppressed both G(2) arrest and apoptosis.

6184- Cuc,    Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells
- vitro+vivo, PC, NA
TumCG↓, cucurbitacin B was tested in vitro and in vivo against human pancreatic cancer cells. Dose-response studies showed that the drug inhibited 50% growth of seven pancreatic cancer cell lines at 10(-7) mol/L,
TumCCA↑, Cucurbitacin B caused dose- and time-dependent G(2)-M-phase arrest and apoptosis of pancreatic cancer cells.
Apoptosis↑,
JAK2↓, associated with inhibition of activated JAK2, STAT3, and STAT5, increased level of p21(WAF1) even in cells with nonfunctional p53, and decrease of expression of cyclin A, cyclin B1, and Bcl-XL with subsequent activation of the caspase cascade.
STAT3↓,
STAT5↓,
P21↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
Bcl-xL↓,
ChemoSen↑, combination of cucurbitacin B and gemcitabine synergistically potentiated the antiproliferative effects of gemcitabine on pancreatic cancer cells.
TumVol↓, cucurbitacin B decreased the volume of pancreatic tumor xenografts in athymic nude mice by 69.2%
toxicity↓, without noticeable drug toxicities.

477- CUR,    Curcumin induces G2/M arrest and triggers autophagy, ROS generation and cell senescence in cervical cancer cells
- in-vitro, Cerv, SiHa
TumCP↓,
TumCCA↑, Inducing G2/M cell cycle arrest
Apoptosis↑,
TumAuto↑,
CycB/CCNB1↓, cyclins B1
CDC25↓,
ROS↑,
p62↑,
LC3‑Ⅱ/LC3‑Ⅰ↑,
cl‑Casp3↑,
cl‑PARP↑,
P53↑,
P21↑,

118- CUR,    Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
ROS↑, WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells.
Bcl-2↓,
PARP↑,
cDC2↓, decreased expression of CDC2, cyclinB1, and MDM2
CycB/CCNB1↓,
MDM2↓,
eff↓, Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis,
eIF2α↑, WZ35 treatment also induced a constant increase in the level of phosphorylated eIF2α 3 to 12 h after WZ35 treatment
ATF4↑, ATF4 expression also increased in a similar manner with p-eIF2α
CHOP/DDIT3↑, CHOP protein expression apparently increased 9-24 h after WZ35 treatment and peaked at 12 h
ER Stress↑, results suggest that WZ35 can induce ER stress in prostate cancer cells
TumCCA↑, WZ35 induced cell cycle arrest in G2/M phase in PC-3 cells

6214- CUR,    Curcumin Nanoparticles-related Non-invasive Tumor Therapy, and Cardiotoxicity Relieve
TumCD↓, Curcumin plays the antitumor effect by directly promoting tumor cell death and reducing tumor cells' invasive ability.
TumCI↓,
*Inflam↓, curcumin has many pharmacological effects, such as anti-inflammation, antioxidation, antitumor, etc.
*antiOx↓,
*AntiTum↓,
NF-kB↓, Curcumin exerts the therapeutic effect mainly by inhibiting the nuclear factor-κB (NF-κB) signal pathway, inhibiting the production of cyclooxygenase-2 (COX-2),
COX2/PTGS2↓,
Casp9↓, promoting the expression of caspase-9, and directly inducing reactive oxygen species (ROS) production in tumor cells.
ROS↑, Curcumin can induce lethal levels of reactive oxygen species (ROS) in tumors
BioAv↑, Curcumin nanoparticles can solve curcumin's shortcomings, such as poor water solubility and high metabolic rate, and can be effectively used in antitumor therapy.
RadioS↑, Figure 1, Curcumin Increases Radiosensitivity of Tumor
ChemoSen↑,
Imm↑,
PhotoS↑, Curcumin Mediates the Antitumor Effect of PDT
sonoS↑, Curcumin Mediates the Antitumor Effect of SDT
5LO↓, down-regulating the activities of cyclooxygenase-2 (COX-2), lipoxygenase (LOX), inducible nitric oxide synthase (iNOS) and so on, reducing the production of proinflammatory cytokines such as IL-2, tumor necrotic factor-α (TNF-α),
iNOS↓,
IL2↓,
TNF-α↓,
Casp9↑, activating intracellular caspase-9 and caspase-3, reducing the expression of p53, inhibiting Bcl2, and promoting the expression of Bax and down-regulating the proportion of Bcl2/Bax
Casp3↑,
Bcl-2↓,
BAX↑,
Apoptosis↑, promote apoptosis by activating caspase-4 and stimulating the Endoplasmic reticulum (ER) stress pathway and mitochondria stress pathway in tumor cells [
ER Stress↑,
cycD1/CCND1↓, It reduces the expression of cyclin D1, cyclin kinase-dependent kinase 2 (CDK2), cdc2/cyclin B complex, and other cell cycle-related proteins,
CDK2↓,
CycB/CCNB1↓,
TumCCA↑, blocks tumor cells from G1 / S phase and G2 / M phase, thus exerting an antitumor effect
MMPs↓, curcumin inhibits tumor invasion and metastasis by inhibiting NF-κB and other signaling pathways, such as chemokine and matrix metalloproteinases (MMPs)
*radioP↑, Curcumin can effectively treat and prevent radiation adverse reactions such as radiation dermatitis and radiation pneumonia by reducing the expression of inflammatory factors such as fibrotic cytokines, TNF-α, and IL-1, inhibiting NF-κB signal pathwa
chemoP↑, Protective Effect of Curcumin on Side Effects of Chemotherapy
hepatoP↑, urcumin alleviates the hepatotoxicity caused by chemotherapy through anti-inflammation and antioxidation, reducing the level of liver fibrosis and blood lipids [
cardioP↑, Using curcumin to reduce the cardiotoxicity of chemotherapy can improve the therapeutic effect of tumors and patients' prognosis and quality of life.
eff↑, Curcumin Enhances the Therapeutic Effect of Immunotherapy
PhotoS↑, it has the potential to be a new photosensitizer
eff↑, Curcumin nanoparticles with functions of relieving hypoxia and consuming GSH could improve the ability of curcumin to induce ROS and promote ROS- mediated tumor cell death
ROS↑,
GSH↓,

6281- DL,    Applications of Limonene in Neoplasms and Non-Neoplastic Diseases
- Review, Var, NA - Review, AD, NA - Review, Diabetic, NA
*antiOx↑, spanning antioxidant, anti-inflammatory, antitumor, antidiabetic, neuroprotective, and gastroprotective domains.
AntiTum↑,
*AntiDiabetic↑,
*neuroP↑, The neuroprotective potential of limonene has been demonstrated in different neurodegenerative diseases (NDs), including multiple sclerosis, stroke, epilepsy, Alzheimer’s disease (AD), and anxiety
*GastroP↑,
*ROS↓, we explore its molecular mechanisms, ranging from reactive oxygen species mitigation
*toxicity↓, Its low toxicity and high bioavailability support its potential as a safe adjunct or alternative in phytotherapy.
*BioAv↑,
ChemoSen↑, combining limonene with tamoxifen increases the anticancer efficacy by inducing apoptosis in MCF 7 BC cells
BAX↑, MCF-7 cells, D-limonene treatment significantly increases the expression of Bcl-2-associated X protein (Bax) and p53 while downregulating Bcl-2, inducible nitric oxide synthase (iNOS), and COX-2
P53↓,
Bcl-2↓,
iNOS↓,
COX2/PTGS2↓,
eff↑, IC50 of free limonene was reported to be 985.00 μg/mL, whereas its encapsulation in chitosan nanoparticles (LimChiNPs) significantly reduced the IC50 to 650.70 μg/mL.
ROS↑, Furthermore, this dual therapy augmented intracellular reactive oxygen species production and promoted cell cycle arrest predominantly at the G1 phase via the modulation of cyclin D1 and B1 [20].
TumCCA↑,
cycD1/CCND1↓,
CycB/CCNB1↓,
TumCMig↓, migration capacity of MCF-7 cells was also markedly inhibited under the combined regimen, suggesting potential to curb metastatic progression
*lipid-P↓, Limonene therapy resulted in a decrease in lipid peroxidation levels and an increase in the level of glutathione, a major antioxidant that helps protect cells from damage
*GSH↑,
*SOD↑, Moreover, the activity of antioxidant enzymes (SOD and glutathione peroxidase (GPx)) was improved, indicating that the body’s natural defense system was functioning better again
*GPx↑,
*hepatoP↑, limonene treatment has been shown to mitigate liver damage caused by DEN/2-AAF exposure by reinforcing the antioxidant defenses in hepatic cells
*glucose↓, D-limonene consistently lowered fasting glucose and HbA1c, improved lipid profiles, and enhanced antioxidant defenses (e.g., increased SOD, CAT, and GSH levels)
*AGEs↓, D-limonene has been shown to inhibit the formation of advanced glycation end products (AGEs) through multiple mechanisms,
*Obesity↓, Notably, limonene also stimulates differentiation and glucose uptake in adipocytes, suggesting a role in counteracting insulin resistance and obesity-related metabolic dysfunction
*Aβ↓, The neuroprotective properties of limonene find expression in suppressing Aβ-induced cell death and decreasing ROS levels
*AChE↓, Further insights into the molecular mechanism of limonene’s inhibition of AChE have been provided by molecular dynamics simulations

6276- DL,  Tam,    Combination of tamoxifen and D-limonene enhances therapeutic efficacy in breast cancer cells
- in-vitro, BC, MCF7
TumCG↓, D-limonene has been reported to inhibit the growth of certain malignancies significantly.
tumCV↓, combined effects of tamoxifen with D-limonene have shown significant decrease in the cell viability of MCF 7 cells.
TumCCA↑, arrested at G1 phase by regulating cyclin D1 and cyclin B1
cycD1/CCND1↓,
CycB/CCNB1↓,
Apoptosis↑, combining D-limonene and tamoxifen might increase the anticancer efficacy by inducing apoptosis in MCF 7 breast cancer cells.

1328- EMD,    Emodin induces apoptosis of human tongue squamous cancer SCC-4 cells through reactive oxygen species and mitochondria-dependent pathways
- in-vitro, Tong, SCC4
TumCCA↑, G2/M arrest
P21↑,
Chk2↑,
CycB/CCNB1↓,
cDC2↓,
Apoptosis↑,
Cyt‑c↑, release of cytochrome c from mitochondria
Casp9↑,
Casp3↑,
ROS↑,
MMP↓,
Bax:Bcl2↑,
ER Stress↑,

6836- EMD,    Emodin and the Anthraquinone Scaffold: Therapeutic Promise and Strategies to Overcome Translational Barriers
- Review, Nor, NA
*antiOx↑, graphic abstract
*neuroP↑,
*Inflam↓,
*hepatoP↑,
AntiTum↑,
*Bacteria↓,
*diuretic↑,
*AntiDiabetic↑,
*BioAv↝, formulation composition and herb–herb or herb–drug interactions are critical determinants of anthraquinone bioavailability and, ultimately, therapeutic outcomes.
*NF-kB↓, figure 4
*AMPK↑,
*JAK↓,
*STAT3↓,
*ROS↓, At low to moderate concentrations, particularly in models of inflammatory or oxidative tissue injury, emodin exerts net antioxidant and cytoprotective effects by lowering ROS levels, limiting lipid peroxidation, and enhancing endogenous antioxidant d
*lipid-P↓,
ROS↑, in cancer cells and other metabolically stressed conditions, the anthraquinone scaffold has been reported to act predominantly as a pro-oxidant, shifting redox homeostasis toward oxidative stress and promoting intracellular ROS accumulation,
TumCCA↑, In human colon cancer (WiDr) cells, aloe-emodin induced a pronounced G2/M arrest associated with suppression of cyclin B1, a critical regulator of mitotic entry.
CycB/CCNB1↓,
BAX↑, upregulation of Bax and Bak alongside the downregulation of anti-apoptotic members such as Bcl-2 and Bcl-xL.
Bcl-2↓,
MOMP↑, As a result, mitochondrial outer-membrane permeabilization (MOMP) is promoted, enabling cytochrome c release and subsequent apoptosome formation through association with Apaf-1.
Cyt‑c↑,
Casp9↑, Activation of initiator caspase-9 follows, triggering executioner caspases, notably caspase-3 and caspase-7, and culminating in apoptotic cell death
Casp3↑,
Casp7↑,
Apoptosis↑,
P53↑, where emodin-induced ROS accumulation and p53 activation contribute to the inhibition of pathological proliferation relevant to restenosis and atherosclerotic remodeling

6389- Eug,    Molecular Insights into the Management of Eugenol's Anticancer Action Against Colon Cancer: A Detailed Review
- Review, Colon, NA
Apoptosis↓, Eugenol’s multitargeted action encompasses apoptosis induction, cell cycle arrest, suppression of inflammatory pathways, and inhibition of metastatic progression.
TumCCA↓,
Inflam↓,
TumMeta↓,
BioAv↑, nanotechnological encapsulation strategies have been explored to enhance bioavailability and pharmacokinetic stability.
eff↓, The compound is susceptible to oxidation when exposed to light, atmospheric oxygen, and elevated temperatures[2].
Half-Life↓, eugenol undergoes rapid absorption across the gastrointestinal epithelium, entering the systemic circulation within 30-60 minutes[3]. The swift absorption profile, while ensuring bioavailability, paradoxically limits it therapeutic effectiveness
*ROS↓, eugenol inhibits the endogenous production of reactive oxygen species (ROS) and reactive nitrogen species (RNS)
*RNS↓,
*SOD↓, Eugenol augments the body’s intrinsic antioxidant defense mechanisms, elevating expression of cytoprotective enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferases (GSTs)
*Catalase↑,
*GSTs↑,
*MAOA↓, Through monoamine oxidase (MAO) inhibition, eugenol modulates neurotransmitter homeostasis in the central nervous system, offering neuroprotective benefit
*neuroP↑,
*DNAdam↓, By eliminating reactive molecular species and preventing accumulation of damaged DNA and proteins, eugenol reduces the likelihood of mutations
Apoptosis↑, Multiple investigations have demonstrated eugenol’s capacity to induce apoptosis in diverse colon cancer cell lines, including HT-29, HCT-116, Caco-2, and SW-620
ROS↑, In human promyelocytic leukemia cells (HL-60) and colorectal cancer models, eugenol triggers elevated intracellular ROS accumulation
selectivity↑, This pro-oxidant activity in cancer cells contrasts sharply with eugenol’s cytoprotective antioxidant effects in normal cells, illustrating its selective anticancer action
MMP↓, Loss of mitochondrial membrane integrity triggers cytochrome c release into the cytosol, activating the caspase-9/caspase-3 cascade and culminating in programmed cell death
Cyt‑c↓,
Casp3↑,
Casp9↑,
TumCD↑,
BAX↑, Eugenol enhances expression of the tumor suppressor protein p53, which transactivates pro-apoptotic genes (BAX, BAD, APAF-1) while suppressing anti-apoptotic genes (BCL-2, BCL-XL)
BAD↑,
APAF1↑,
Bcl-2↓,
Bcl-xL↓,
P53↑,
cl‑PARP↑, eugenol activates executioner caspases-3 and -7, facilitating cleavage of critical substrates (PARP, DFF45) and morphological manifestations of apoptosis
TumCCA↑, Eugenol-treated cancer cells exhibit accumulation at the G2/M phase transition, accompanied by downregulation of cell cycle-promoting proteins (cyclin D1, cyclin B1, CDK2, CDK4) and upregulation of CDK inhibitors (p21, p27)
cycD1/CCND1↓,
CycB/CCNB1↓,
CDK2↓,
CDK4↓,
P21↑,
p27/CDKN1B↑,
NF-kB↓, Eugenol inhibits IκB-α phosphorylation, preventing NF-κB nuclear translocation and transcriptional activity[
COX2/PTGS2↓, Eugenol downregulates COX-2 expression, reducing pro-tumorigenic prostaglandin production and associated inflammation[3]
PGE2↓,
MAPK↓, Suppression of MAPK cascade reduces cancer cell proliferation and survival
PI3K↓, PI3K/Akt/mTOR Pathway Blockade
Akt↓,
mTOR↓,
MMPs↓, Eugenol suppresses MMP expression and activity, reducing tumor cell invasive capacity
EMT↓, Eugenol suppresses EMT-promoting transcription factors (Snail, Slug, ZEB1), maintaining E-cadherin expression and cellular adhesion[5].
Snail↓,
Slug↓,
Zeb1↓,
E-cadherin↑,
ChemoSen↑, Emerging evidence suggests eugenol enhances anticancer efficacy of conventional chemotherapeutic agents[5][6].

6386- Eug,    A comprehensive and systematic review on potential anticancer activities of eugenol: From pre-clinical evidence to molecular mechanisms of action
- Review, Var, NA
Apoptosis↑, Eugenol exhibits significant anticancer effects in a variety of biological pathways, namely apoptosis, autophagy, cell cycle progression, inflammation, invasion, and metastasis.
TumAuto↑,
TumCCA↑,
Inflam↝,
TumCI↓,
TumMeta↓,
cycD1/CCND1↓, It decreases the expression of cyclin D1, cyclin B, proliferating cell nuclear antigen, nuclear factor-ƙB, inhibitor of nuclear factor ƙB, and B-cell lymphoma-2.
CycB/CCNB1↓,
PCNA↓,
NF-kB↓,
Bcl-2↓,
BAX↑, Eugenol increases the expression of B-cell lymphoma-2 (BCL-2) associated X, BH3-interacting domain death agonist, BCL-2 associated agonist of cell death, apoptotic protease activating factor 1, cytochrome c, p21, and p53.
AIF↑,
P21↑,
P53↑,
ChemoSen↑, use of eugenol alone or along with other chemotherapeutic anticancer agents is found to be very effective in cancer therapy.

6856- FBZ,    Fenbendazole Suppresses Growth and Induces Apoptosis of Actively Growing H4IIE Hepatocellular Carcinoma Cells via p21-Mediated Cell-Cycle Arrest
- in-vitro, Liver, H4IIE
TumCCA↑, The number of cells was markedly increased in sub-G1 phase but decreased in S- and G2/M phases by FZ.
P21↑, FZ up-regulated p21 (an inhibitor of cyclin-CDK) but suppressed the expression of cell cycle-promoting proteins (cyclin D1 and cyclin B1). FZ did not affect integrin αV or n-cadherin expression as well as cell migration.
cycD1/CCND1↓,
CycB/CCNB1↓,
GlucoseCon∅, Glycolytic changes (glucose consumption and lactate production) and the generation of reactive oxygen species (ROS) were not affected by FZ.
lactateProd∅,
ROS∅,
selectivity↑, FZ selectively suppressed the growth of cells via p21-mediated cell cycle arrest at G1/S and G2/M, and resulted in apoptosis only in actively growing cells but not in quiescent cells.

6853- FBZ,    Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer cell death by modulating multiple cellular pathways
- vitro+vivo, Lung, A549 - in-vitro, Lung, H460
TumCD↑, exerts cytotoxicity to human cancer cells at micromolar concentrations.
P53↑, Simultaneously, it caused mitochondrial translocation of p53 and effectively inhibited glucose uptake, expression of GLUT transporters as well as hexokinase (HK II) - a key glycolytic enzyme that most cancer cells thrive on.
GlucoseCon↓,
GLUT4↓, FZ exposure reduced the expression of Glut-4 transporter as well as hexokinase (HK II), which may be linked to p53 activation and alteration of microtubule dynamics
HK2↓,
TumCG↓, It blocked the growth of human xenografts in nu/nu mice model when mice were fed with the drug orally.
P-gp/ABCB1∅, treated and untreated cells showed comparable levels of Rho123 accumulation affirming that FZ is not a substrate or inhibitor of P-gp.
TumCCA↑, FZ treatment results in early G2/M block accompanied by cell death
CycB/CCNB1↓, simultaneous decrease in cyclin B1 levels
eff↑, Tumour cell lines with wild-type p53 show enhanced sensitivity to FZ induced apoptosis
selectivity↑, Remarkably, FZ showed less toxicity towards primary epithelial cells cultured from rat lung tissue as compared to a lung cancer cell line
MMP↓, Correspondingly, mitochondrial membrane depolarization
lactateProd↓, FZ treatment also resulted in reduced lactate levels (Fig. 8c). Hence, FZ induced cell death appeared to be related to inhibition of glucose uptake.
eff↑, we conclude that FZ shows synergistic effect with DCA, 2DG and over a range of doses with taxol.
Dose↝, A549 cells and mice bearing tumours (2–3 mm) were fed with FZ (1 mg/mouse) orally every second day for 12 days
TumCG↓, FZ inhibits tumour cell growth in vivo by inducing apoptosis of tumour cells.

6901- FIS,    Fisetin induces G2/M phase arrest and caspase-mediated cleavage of p21Cip1 and p27Kip1 leading to apoptosis and tumor growth inhibition in HNSCC
- in-vivo, HNSCC, CAL33
TumCG↓, fisetin (25-75 µM for 24-48 h) dose-dependently inhibited growth and induced death in HNSCC Cal33 and UM-SCC-22B cells
TumCD↑,
selectivity↑, without showing any death in normal cells
TumCCA↑, Fisetin (25-50 µM) induced G2/M phase arrest via decrease in Cdc25C, CDK1, cyclin B1 expression, and an increase in p53(
CDC25↓,
CDK1↓,
CycB/CCNB1↓,
P53↑,
DNAdam↑, concentration-dependent increase in fisetin-induced DNA damage and apoptosis in HNSCC cells was authenticated by comet assay, gamma-H2A.X
Apoptosis↑,
γH2AX↑,
cl‑PARP↑, marked cleavage of PARP protein
other↝, Interestingly, fisetin-induced cell death occurred independently of p53 and reactive oxygen species production.
JNK↑, activation of JNK and inhibition of PI3K/Akt, ERK1/2, EGFR, and STAT-3 signaling were identified.
PI3K↓,
Akt↓,
ERK↓,
EGFR↓,
STAT3↓,
TumAuto↑, fisetin was also found to induce autophagy; nevertheless, autophagy attenuation exaggerated apoptosis.
Dose↝, Oral fisetin (50 mg/kg body weight) treatment to establish Cal33 xenograft in mice for 19 days showed 73% inhibition in tumor volume (p < 0.01) along with a decrease in Ki67-positive cells and an increase in cleaved caspase-3 level in tumors.
TumVol↓,
Ki-67↓,
cl‑Casp3↑,
P21↓, protein levels of p21Cip1 and P27Kip1 were also decreased by fisetin in tumors.
p27/CDKN1B↓,

6982- Form,    Formononetin: A Review of Its Anticancer Potentials and Mechanisms
- Review, Var, NA
AntiTum↑, Formononetin elicits antitumorigenic properties in vitro and in vivo by modulating numerous signaling pathways to induce cell apoptosis (by intrinsic pathway involving Bax, Bcl-2, and caspase-3 proteins)
Apoptosis↑,
BAX↑,
Bcl-2↓,
Casp3↑,
TumCCA↑, cell cycle arrest (by regulating mediators like cyclin A, cyclin B1, and cyclin D1),
cycA1/CCNA1↓,
CycB/CCNB1↓,
cycD1/CCND1↓,
TumCP↓, suppress cell proliferation [by signal transducer and activator of transcription (STAT) activation, phosphatidylinositol 3-kinase/protein kinase-B (PI3K/AKT), and mitogen-activated protein kinase (MAPK) signaling pathway],
VEGF↓, inhibit cell invasion [by regulating growth factors vascular endothelial growth factor (VEGF) and Fibroblast growth factor 2 (FGF2), and matrix metalloproteinase (MMP)-2 and MMP-9 proteins].
FGF↓,
MMP2↓,
MMP9↓,
eff↑, Co-treatment with other chemotherapy drugs such as bortezomib, LY2940002, U0126, sunitinib, epirubicin, doxorubicin, temozolomide, and metformin enhances the anticancer potential of both formononetin and the respective drugs through synergistic effec
ChemoSen↑,
chemoPv↑, Compiling the evidence thus far highlights the potential of formononetin to be a promising candidate for chemoprevention and chemotherapy.
p‑Akt↓, downregulation of EphB3, p-AKT, p-P13K, p-STAT3, inhibition of cyclin D1, MMP2/9
p‑STAT3↑,
TumCMig↓, MDA-MB-231-luc and 4T1 Inhibition of cell migration and invasion, elevation of TIMP-1 and TIMP-2, and suppression of PI3K/AKT signaling
TumCI↓,
TIMP1↑,
TIMP2↑,
PI3K↓,
Akt↓,
Dose↝, formononetin is administered into the mice intraperitoneally or intragastrically, mainly at doses between 10 and 60 mg/kg for 2–3 weeks via intraperitoneal route and between 15 and 100 mg/kg for more than a month via intragastric route
TumCG↓, In general, the formononetin treatment suppresses xenograft tumor growth in terms of tumor weight and volume, and also inhibits tumor invasiveness and angiogenesis.
TumW↓,
TumVol↓,
angioG↓,
Casp3↑, After exposure to formononetin, expression levels of cleaved caspase-3 and -9 in ovarian cancer cells increased in a dose-dependent manner
Casp9↑,
cl‑PARP↑, leading to the cleavage of poly(ADP-ribose) polymerase (PARP), which results in the inability to repair damaged DNA
DNArepair↓,
MMP↓, significant loss of mitochondrial membrane potential of approximately 457% (P < 0.001) and 265% (P < 0.001) in ES2 and OV90 ovarian cancer cells was observed upon exposure to 40 µM formononetin
BAX↑, expression of Bax protein surged upon formononetin treatment, while Bcl-2 protein level decreased
Bcl-2↓,
DR5↑, formononetin displayed high affinity and steric compatibility to death receptor 5, which could be activated to mediate the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis
ROS↑, Formononetin can also induce the apoptotic pathway via the overexpression of reactive oxygen species (ROS) and disturbance of the intracellular antioxidant system.
eff↓, abrogated with the use of antioxidants such as N-acetyl-L-cysteine (NAC) and glutathione (GSH), suggesting that formononetin induces apoptosis via ROS production.
p‑ERK↓, formononetin was demonstrated to be a promising molecule that inhibits the phosphorylation of ERK1/2 itself as well as the phosphorylation of downstream ERK substrate (P90RSK)
PTEN↑, Besides the inhibition on AKT activity, formononetin upregulated PTEN expression in bladder cancer T24 cell.
Hif1a↓, The inhibition of AKT pathway by formononetin was mediated through the attenuation of HIF-α expression and inflammatory cytokines release
eff↑, Formononetin was shown to potentiate bortezomib-induced apoptosis in multiple myeloma
eff↑, synergistic effect was evident between formononetin and metformin in cancer treatment.
ChemoSen↑, sensitivity of glioma cells towards doxorubicin was shown to be enhanced by co-treatment with formononetin
HDAC↓, formononetin in doxorubicin-treated glioma cells was associated with formononetin’s suppressive effect on the histone deacetylase (HDAC) 5 expression
*BioAv↑, Due to its lipophilic nature, formononetin is rapidly absorbed into the gut via passive diffusion, with a peak absorption at 30 min ().
*Half-Life↝, Formononetin was determined to have a half-life of ∼2–3 h after oral administration and ∼2 h after intravenous administration
*BioAv↝, At oral administration of formononetin at 20–50 mg/kg, the peak plasma concentration was achieved between (Tmax) 0.5–1 h, while the maximum plasma concentration (Cmax) was determined ranging from 62 nM (17 ng/ml) to 302 nM (81 ng/ml).
*BioAv↑, Meanwhile, the Cmax of 1,302.8 nM (349.5 ng/ml) and 16,956.6 nM (4,548.5 ng/ml) was achieved after intravenous administration of formononetin at 4 and 10 mg/kg, respectively
*BioAv↑, rapidly metabolized and extensively converted into its metabolites daidzein and conjugates of daidzein and formononetin to be excreted, which makes it poorly bioavailable.
*eff↑, Drug delivery systems are strategies employed to overcome the low bioavailability and low water solubility of formononetin to achieve its pharmacological efficacy at minimum dose

7086- GAR,    Garcinol: An emerging epigenetic modifier with versatile anticancer properties
- Review, Var, NA
AntiCan↑, garcinol has demonstrated huge potential as an anti-cancer agent, inhibiting tumor growth, progression, and metastasis in various cancers, such as lung, liver, pancreas, prostate, breast, colon, and brain cancers.
TumCG↓,
TumMeta↓,
toxicity↓, garcinol offers a safer alternative with broad-spectrum activity and minimal adverse effects.
Apoptosis↑, anti-tumorigenic properties are linked to apoptosis induction, angiogenesis inhibition, and modulation of the tumor microenvironment
angioG↓,
*BioAv↝, nano-delivery systems have improved its bioavailability and therapeutic efficacy, overcoming challenges related to its solubility and stability.
HATs↓, Garcinol primarily targets histone acetyltransferases (HATs), particularly p300 and CBP (CREB-binding protein), leading to structural modifications in these proteins.
p300↓,
CBP↓,
PI3K↓, Garcinol exerts its anticancer effects primarily by modulating key signaling pathways, including the PI3K/AKT, NF-κB, JAK/STAT, and MAPK pathways.
Akt↓,
NF-kB↓,
STAT↓,
mTOR↓, figure 1
DFF45↓,
survivin↓,
N-cadherin↓,
Twist↓,
MMP2↓,
MMP3↓,
MMP9↓,
Mcl-1↓,
EZH2↓,
NOTCH↓,
CXCR4↓,
PGE2↓,
VEGF↓,
mPGES-1↓,
CycB/CCNB1↓,
CDK2↓,
CDK4/6↓,
iNOS↓,
COX2/PTGS2↓,
IL1↓,
TNF-α↓,
PARP↑,
Bcl-2↓,

804- GAR,    Garcinol inhibits the proliferation of endometrial cancer cells by inducing cell cycle arrest
- in-vitro, EC, HEC1B - in-vitro, EC, ISH
TumCP↓,
TumCCA↑, induced ISH and HEC-1B cell cycle arrest at the G1 phase and G2/M phase, respectively
P53↑,
P21↑,
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
CycB/CCNB1↓,
p‑cJun↑,

7103- GEN,    A Comprehensive Review of Genistein's Effects in Preclinical Models of Cervical Cancer
- Review, Cerv, NA
TumCP↓, genistein inhibits cervical cancer cell proliferation and induces apoptosis
Apoptosis↑,
RadioS↑, Use of genistein in combination with radiation or chemotherapy agents resulted in enhanced response indicating radio- and chemo-sensitization properties.
ChemoSen↑,
*antiOx↑, evidence that genistein has antioxidant [17], anti-inflammatory [18], antibacterial [19], antiviral [20,21], antidiabetic [22,23], neuroprotective [24,25], and anti-cancer [26,27,28] effects.
*Inflam↓,
*Bacteria↓,
*AntiViral↑,
*AntiDiabetic↑,
*neuroP↑,
AntiCan↑,
TumCG↓, genistein had reduced cell growth and invasion, and increased cell cycle arrest and apoptosis
TumCI↓,
TumCCA↑,
cl‑PARP↑, increased levels of cleaved poly (ADP-ribose) polymerase (PARP), a marker of apoptosis, after treatment with genistein in HeLa cells,
selectivity↑, while no cleaved PARP was seen in L929 cells (normal mouse fibroblasts).
CycB/CCNB1↓, decreased protein expression of cyclin B1 and cyclin-dependent kinase 1 (CDK1), and decreased tyrosine phosphorylation of cell division control protein 2 (cdc2)
CDK1↓,
p‑cDC2↓,
p‑ERK↓, genistein inhibits cell growth and decreases cell viability through decreasing the phosphorylation/activation of ERK, while increasing phosphorylation/activation of p38 and JNK
p‑p38↑,
p‑JNK↑,
MMP9↓, decrease in mRNA expression of MMP-9 and an increase in TIMP-1 expression
TIMP1↑,
BioAv↓, Genistein has low solubility and bioavailability.
BioAv↑, Nanoparticle technology has been employed for the encapsulation and delivery of compounds with low absorption and bioavailability.
Half-Life↑, Despite its low bioavailability, genistein has a long half-life of 46 h in vivo

7730- isoFl,    Anticancer Potential of Isoflavones: A Narrative Overview of Mechanistic Insights and Experimental Evidence from the Past Ten Years
- Review, Var, NA
Apoptosis↑, Reported anticancer effects include induction of apoptosis, ROS generation, cell cycle arrest, inhibition of cell migration and invasion, loss of mitochondrial membrane potential, modulation of estrogen-related pathways, and antiangiogenic activity.
ROS↓,
TumCCA↓,
TumCMig↓,
TumCI↓,
MMP↓,
angioG↓,
ChemoSen↑, synergistic interactions with chemotherapeutic drugs and natural compounds and new drug delivery systems have been described
p‑Akt↓, Apoptosis; Decreased expression of phospho-AKT and phospho-mTOR; PARP cleavage; Reduced Cyclin A/B1 and STAT3 (Y705) activation AsPC-1
p‑mTOR↓,
cl‑PARP↑,
cycA1/CCNA1↓,
CycB/CCNB1↓,
STAT3↓,

7856- isoO,    Isoorientin induces the apoptosis and cell cycle arrest of A549 human lung cancer cells via the ROS‑regulated MAPK, STAT3 and NF‑κB signaling pathways
- in-vitro, Lung, A549
Bacteria↓, Isoorientin (ISO) is a naturally occurring C‑glycosyl flavone that has various pharmacological properties, such as anti‑bacterial and anti‑inflammatory effects
Inflam↓,
TumCD↑, ISO exerted significant cytotoxic effects on 3 lung cancer cell lines, but had no obvious side‑effects on normal cells.
selectivity↑,
Apoptosis↑, ISO induced mitochondrial‑dependent apoptosis by reducing mitochondrial membrane potential
MMP↓,
BAX↑, ISO also increased the expression levels of Bax, cleaved‑caspase‑3 (cle‑cas‑3) and poly(ADP‑ribose) polymerase (PARP; cle‑PARP), and decreased the expression levels of Bcl‑2 in A549 cells.
cl‑Casp3↑,
PARP↓,
Bcl-2↓,
TumCCA↑, ISO induced G2/M cell cycle arrest by decreasing the expression levels of cyclin B1 and CDK1/2, and increasing the expression levels of p21 and p27 in A549 cells.
CycB/CCNB1↓,
CDK1↓,
CDK2↓,
NA↑,
p27/CDKN1B↑,
ROS↑, As the duration of ISO treatment increased, intracellular reactive oxygen species (ROS) levels in A549 cells also increased.
eff↓, pre‑treatment of the cells with the ROS scavenger, N‑acetylcysteine (NAC), inhibited ISO‑induced apoptosis.
p‑p38↑, ISO increased the expression levels of p‑p38, p‑JNK and IκB‑α; and decreased the expression levels of p‑extracellular signal‑regulated kinase (ERK), p‑signal transducer and activator of transcription (STAT)3, (NF)‑κB
p‑JNK↑,
ERK↓,
STAT3↓,
NF-kB↓,

863- Lae,    Amygdalin inhibits the growth of renal cell carcinoma cells in vitro
- in-vitro, RCC, NA
TumCG↓,
TumCP↓,
TumCCA↑, cell cycle arrest in the S-phase
CDK1↓,
CycB/CCNB1↓,
E-cadherin↝,
N-cadherin↝,

2914- LT,    Therapeutic Potential of Luteolin on Cancer
- Review, Var, NA
*antiOx↑, As an antioxidant, Luteolin and its glycosides can scavenge free radicals caused by oxidative damage and chelate metal ions
*IronCh↑,
*toxicity↓, The safety profile of Luteolin has been proven by its non-toxic side effects, as the oral median lethal dose (LD50) was found to be higher than 2500 and 5000 mg/kg in mice and rats, respectively, equal to approximately 219.8−793.7 mg/kg in humans
*BioAv↓, One major problem related to the use of flavonoids for therapeutic purposes is their low bioavailability.
*BioAv↑, Resveratrol, which functions as the inhibitor of UGT1A1 and UGT1A9, significantly improved the bioavailability of Luteolin by decreasing the major glucuronidation metabolite in rats
DNAdam↑, Luteolin’s anticancer properties, which involve DNA damage, regulation of redox, and protein kinases in inhibiting cancer cell proliferation
TumCP↓,
DR5↑, Luteolin was discovered to promote apoptosis of different cancer cells by increasing Death receptors, p53, JNK, Bax, Cleaved Caspase-3/-8-/-9, and PARP expressions
P53↑,
JNK↑,
BAX↑,
cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↑,
survivin↓, downregulating proteins involved in cell cycle progression, including Survivin, Cyclin D1, Cyclin B, and CDC2, and upregulating p21
cycD1/CCND1↓,
CycB/CCNB1↓,
CDC2↓,
P21↑,
angioG↓, suppress angiogenesis in cancer cells by inhibiting the expression of some angiogenic factors, such as MMP-2, AEG-1, VEGF, and VEGFR2
MMP2↓,
AEG1↓,
VEGF↓,
VEGFR2/KDR/Flk1↓,
MMP9↓, inhibit metastasis by inhibiting several proteins that function in metastasis, such as MMP-2/-9, CXCR4, PI3K/Akt, ERK1/2
CXCR4↓,
PI3K↓,
Akt↓,
ERK↓,
TumAuto↑, can promote the conversion of LC3B I to LC3B II and upregulate Beclin1 expression, thereby causing autophagy
LC3B-II↑,
EMT↓, Luteolin was identified to suppress the epithelial to mesenchymal transition by upregulating E-cadherin and downregulating N-cadherin and Wnt3 expressions.
E-cadherin↑,
N-cadherin↓,
Wnt↓,
ROS↑, DNA damage that is induced by reactive oxygen species (ROS),
NICD↓, Luteolin can block the Notch intracellular domain (NICD) that is created by the activation of the Not
p‑GSK‐3β↓, Luteolin can inhibit the phosphorylation of the GSK3β induced by Wnt, resulting in the prevention of GSK3β inhibition
iNOS↓, Luteolin in colon cancer and the complications associated with it, particularly the decreasing effect on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)
COX2/PTGS2↓,
NRF2↑, Luteolin has been identified to increase the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), which is a crucial transcription factor with anticarcinogenic properties related
Ca+2↑, caused loss of the mitochondrial membrane action potential, enhanced levels of mitochondrial calcium (Ca2+),
ChemoSen↑, Luteolin enhanced the effect of one of the most effective chemotherapy drugs, cisplatin, on CRC cells
ChemoSen↓, high dose of Luteolin application negatively affected the oxaliplatin-based chemotherapy in a p53-dependent manner [52]. They suggested that the flavonoids with Nrf2-activating ability might interfere with the chemotherapeutic efficacy of anticancer
IFN-γ↓, decreased the expression of interferon-gamma-(IFN-γ)
RadioS↑, suggested that Luteolin can act as a radiosensitizer, promoting apoptosis by inducing p38/ROS/caspase cascade
MDM2↓, Luteolin treatment was associated with increased p53 and p21 and decreased MDM4 expressions both in vitro and in vivo.
NOTCH1↓, Luteolin suppressed the growth of lung cancer cells, metastasis, and Notch-1 signaling pathway
AR↓, downregulating the androgen receptor (AR) expression
TIMP1↑, Luteolin inhibits the migration of U251MG and U87MG human glioblastoma cell lines by downregulating MMP-2 and MMP-9 and upregulating the tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2.
TIMP2↑,
ER Stress↑, Luteolin caused oxidative stress and ER stress in the Hep3B cells,
CDK2↓, Luteolin’s ability to decrease Akt, polo-like kinase 1 (PLK1), cyclin B1, cyclin A, CDC2, cyclin-dependent kinase 2 (CDK2) and Bcl-xL
Telomerase↓, Luteolin dose-dependently inhibited the telomerase levels and caused the phosphorylation of NF-κB and the target gene of NF-κB, c-Myc to suppress the human telomerase reverse transcriptase (hTERT)
p‑NF-kB↑,
p‑cMyc↑,
hTERT/TERT↓,
RAS↓, Luteolin was found to suppress the expressions of K-Ras, H-Ras, and N-Ras, which are the activators of PI3K
YAP/TEAD↓, Luteolin caused significant inhibition of yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ)
TAZ↓,
NF-kB↓, Luteolin was found to have a strong inhibitory effect on the NF-κB
NRF2↓, Luteolin-loaded nanoparticles resulted in a significant reduction in the Nrf2 levels compared to Luteolin alone.
HO-1↓, The expressions of the downstream genes of Nrf2, Ho1, and MDR1 were also reduced, where inhibition of Nrf2 expression significantly increased the cell death of breast cancer cells
MDR1↓,

2916- LT,    Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies
- Review, Var, NA - Review, AD, NA - Review, Park, NA
proCasp9↓, , by inactivating proteins; such as procaspase‐9, CDC2 and cyclin B or upregulation of caspase‐9 and caspase‐3, cytochrome C, cyclin A, CDK2, and APAF‐1, in turn inducing cell cycle
CDC2↓,
CycB/CCNB1↓,
Casp9↑,
Casp3↑,
Cyt‑c↑,
cycA1/CCNA1↑,
CDK2↓, inhibit CDK2 activity
APAF1↑,
TumCCA↑,
P53↑, enhances phosphorylation of p53 and expression level of p53‐targeted downstream gene.
BAX↑, Increasing BAX protein expression; decreasing VEGF and Bcl‐2 expression it can initiate cell cycle arrest and apoptosis.
VEGF↓,
Bcl-2↓,
Apoptosis↑,
p‑Akt↓, reduce expression levels of p‐Akt, p‐EGFR, p‐Erk1/2, and p‐STAT3.
p‑EGFR↓,
p‑ERK↓,
p‑STAT3↓,
cardioP↑, Luteolin plays positive role against cardiovascular disorders by improving cardiac function
Catalase↓, It can reduce activity levels of catalase, superoxide dismutase, and GS4
SOD↓,
*BioAv↓, bioavailability of luteolin is very low. Due to the momentous first pass effect, only 4.10% was found to be available from dosage of 50 mg/kg intake of luteolin
*antiOx↑, luteolin classically exhibits antioxidant features
*ROS↓, The antioxidant potential of luteolin and its glycosides is mainly due to scavenging activity against reactive oxygen species (ROS) and nitrogen species
*NO↓,
*GSTs↑, Luteolin may also have a role in protection and enhancement of endogenous antioxidants such as glutathione‐S‐transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT)
*GSR↑,
*SOD↑,
*Catalase↑,
*lipid-P↓, Luteolin supplementation significantly suppressed the lipid peroxidation
PI3K↓, inhibits PI3K/Akt signaling pathway to induce apoptosis
Akt↓,
CDK2↓, inhibit CDK2 activity
BNIP3↑, upregulation of BNIP3 gene
hTERT/TERT↓, Suppress hTERT in MDA‐MB‐231 breast cancer cel
DR5↑, Boost DR5 expression
Beclin-1↑, Activate beclin 1
TNF-α↓, Block TNF‐α, NF‐κB, IL‐1, IL‐6,
NF-kB↓,
IL1↓,
IL6↓,
EMT↓, Suppress EMT essentially notable in cancer metastasis
FAK↓, Block EGFR‐signaling pathway and FAK activity
E-cadherin↑, increasing E‐cadherin expression by inhibiting mdm2
MDM2↓,
NOTCH↓, Inhibit NOTCH signaling
MAPK↑, Activate MAPK to inhibit tumor growt
Vim↓, downregulation of vimentin, N‐cadherin, Snail, and induction of E‐cadherin expressions
N-cadherin↓,
Snail↓,
MMP2↓, negatively regulated MMP2 and TWIST1
Twist↓,
MMP9↓, Inhibit matrix metalloproteinase‐9 expressions;
ROS↑, Induce apoptosis, reactive oxygen development, promotion of mitochondrial autophagy, loss of mitochondrial membrane potential
MMP↓,
*AChE↓, Reduce AchE activity to slow down inception of Alzheimer's disease‐like symptoms
*MMP↑, Reverse mitochondrial membrane potential dissipation
*Aβ↓, Inhibit Aβ25‐35
*neuroP↑, reduces neuronal apoptosis; inhibits Aβ generation
Trx1↑, luteolin against human bladder cancer cell line T24 was due to induction cell‐cycle arrest at G2/M, downregulation of p‐S6, suppression of cell survival, upregulation of p21 and TRX1, reduction in ROS levels.
ROS↓,
*NRF2↑, Luteolin reduced renal injury by inhibiting XO activity, modulating uric acid transporters, as well as activating Nrf2 HO‐1/NQO1 antioxidant pathways and renal SIRT1/6 cascade.
NRF2↓, Luteolin exerted anticancer effects in HT29 cells as it inhibits nuclear factor‐erythroid‐2‐related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway
*BBB↑, Luteolin can be used to treat brain cancer due to ability of this molecule to easily cross the blood–brain barrier
ChemoSen↑, In ovarian cancer cells, luteolin chemosensitizes the cells through repressing the epithelial‐mesenchymal transition markers
GutMicro↑, Luteolin was also observed to modulate gut microbiota which reduce the number of tumors in case of colorectal cancer by enhancing the number of health‐related microbiota and reduced the microbiota related to inflammation

4778- Lyco,    Lycopene exerts cytotoxic effects by mitochondrial reactive oxygen species–induced apoptosis in glioblastoma multiforme
- in-vitro, GBM, GBM8401
BBB↑, lycopene penetration across the blood-brain barrier and its induction of apoptosis, inhibiting proliferation in GBM8401 and T98G GBM cells
Apoptosis↑,
TumCP↑,
P53↑, lycopene promoted p53 upregulation and suppressed cyclins B and cyclin D, leading to cell cycle arrest through ROS-activated ERK pathways.
CycB/CCNB1↓,
cycD1/CCND1↓,
TumCCA↓,
mt-ROS↑, Lycopene induced Mito-ROS accumulation in GBM cells
TumCG↓, Lycopene inhibits the cell growth of GBM cells

4514- MAG,    Magnolol and its semi-synthetic derivatives: a comprehensive review of anti-cancer mechanisms, pharmacokinetics, and future therapeutic potential
- Review, Var, NA
AntiCan↑, garnered significant interest for its anti-cancer effects
TumCP↓, activities against cancer, affecting various aspects of cancer cell biology, such as proliferation, cell cycle, apoptosis, metastasis, angiogenesis, and signaling pathways, such as NF-κB (Nuclear factor-KappaB), MAPK (Mitogen-activated protein kinase
TumCCA↑,
TumMeta↓,
angioG↓,
NF-kB↓,
MAPK↓,
PI3K↓,
Akt↓,
mTOR↓,
BioAv↓, its low bioavailability and solubility limit its potential clinical application.
*antiOx↑, including anti-oxidant [35], anti-inflammatory, anti-bacterial [36], anti-thrombotic or anti-platelet [37], anti-stress [38], anti-anxiety, anti-Alzheimer [39], Alzheimer, anti-stroke
*Inflam↓,
*AntiAg↑,
ChemoSen↑, administration of MG enhanced the effect of cisplatin in reducing cell viability, self-renewal, and invasion activities in cancer stem cells
cycD1/CCND1↓, Downregulation of Cyclin D1/E/B1, CDK2/4
CycB/CCNB1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
p27/CDKN1B↑, upregulation of p27
P21↑, Upregulation of p21, p53
P53↑,
PTEN↓, Inhibition of PTEN
XIAP↓, Downregulation of XIAP, c-P, and Mc1-1
Mcl-1↓,
Casp3↑, upregulation of Caspase-3/9 NF-κB activity, p-p65, p-MMP-9, and cyclin
Casp9↑,
MMP9↑, Inhibiting MMP-9 through the NF-κB pathway

4537- MAG,    Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action
- in-vivo, Melanoma, NA - in-vitro, Melanoma, A431
*cl‑Casp8↑, Magnolol pretreatment increased the cleavage of caspase-8 and poly-(-ADP-ribose) polymerase (PARP), increased the expression of p21
*PARP↑,
*P21↑,
tumCV↓, Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependent manner
TumCP↓,
TumCCA↑, Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h
CycB/CCNB1↓, decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2
cycA1/CCNA1↓,
CDK4↓,
CDC2↓,
P21↑, simultaneous increase in the expression of Cip/p21, a cyclin-dependent kinase inhibitor.
Apoptosis↑, Magnolol induced apoptosis in vivo and in vitro with an increased cleavage of caspase-8 and PARP.

1782- MEL,    Melatonin in Cancer Treatment: Current Knowledge and Future Opportunities
- Review, Var, NA
AntiCan↑, involvement of melatonin in different anticancer mechanisms
Apoptosis↑, apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases
TumCP↓,
TumCG↑,
TumMeta↑,
ChemoSideEff↓, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy,
radioP↑,
ChemoSen↑, augmentation of the therapeutic effects of conventional anticancer therapies
*ROS↓, directly scavenge ROS and reactive nitrogen species (RNS)
*SOD↑, melatonin can regulate the activities of several antioxidant enzymes like superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase
*GSH↑,
*GPx↑,
*Catalase↑,
Dose∅, demonstrated that 1 mM melatonin concentration is the pharmacological concentration that is able to produce anticancer effects
VEGF↓, downregulatory action on VEGF expression in human breast cancer cells
eff↑, tumor-bearing mice were treated with (10 mg/kg) of melatonin and (5 mg/kg) of cisplatin. The results have shown that melatonin was able to reduce DNA damage
Hif1a↓, MDA-MB-231-downregulation of the HIF-1α gene and protein expression coupled with the production of GLUT1, GLUT3, CA-IX, and CA-XII
GLUT1↑,
GLUT3↑,
CAIX↑,
P21↑, upregulation of p21, p27, and PTEN protein is another way of melatonin to promote cell programmed death in uterine leiomyoma
p27/CDKN1B↑,
PTEN↑,
Warburg↓, FIGURE 3
PI3K↓, in colon cancer cells by downregulation of PI3K/AKT and NF-κB/iNOS
Akt↓,
NF-kB↓,
cycD1/CCND1↓,
CDK4↓,
CycB/CCNB1↓,
CDK4↓,
MAPK↑,
IGF-1R↓,
STAT3↓,
MMP9↓,
MMP2↓,
MMP13↓,
E-cadherin↑,
Vim↓,
RANKL↓,
JNK↑,
Bcl-2↓,
P53↑,
Casp3↑,
Casp9↑,
BAX↑,
DNArepair↑,
COX2/PTGS2↓,
IL6↓,
IL8↓,
NO↓,
T-Cell↑,
NK cell↑,
Treg lymp↓,
FOXP3↓,
CD4+↑,
TNF-α↑,
Th1 response↑, FIGURE 3
BioAv↝, varies 1% to 50%?
RadioS↑, melatonin’s radio-sensitizing properties
OS↑, In those individuals taking melatonin, the overall tumor regression rate and the 5-year survival were elevated


Showing Research Papers: 1 to 50 of 72
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 72

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

NA↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↑, 1,   ATF3↑, 1,   Catalase↓, 1,   GSH↓, 3,   GSR↑, 1,   HO-1↓, 1,   HO-1↑, 1,   lipid-P↑, 2,   NQO1↑, 1,   NRF2↓, 3,   NRF2↑, 2,   ROS↓, 3,   ROS↑, 23,   ROS∅, 2,   i-ROS↑, 1,   mt-ROS↑, 1,   SIRT3↑, 1,   SOD↓, 1,   Trx1↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

ADP:ATP↑, 1,   AIF↑, 1,   ATP↓, 1,   mt-ATP↓, 1,   BOK↑, 1,   CDC2↓, 6,   CDC25↓, 9,   mitResp↓, 1,   MMP↓, 14,   mtDam↑, 1,   Raf↓, 1,   XIAP↓, 2,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

12LOX↓, 1,   AMPK↑, 3,   CAIX↑, 1,   cMyc↓, 2,   p‑cMyc↑, 1,   GlucoseCon↓, 1,   GlucoseCon∅, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,   lactateProd∅, 1,   LDHA↓, 1,   NADPH↑, 1,   PDK1↓, 2,   PDK3↑, 1,   PKM2↓, 1,   p‑S6↓, 1,   Warburg↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 15,   p‑Akt↓, 7,   APAF1↑, 3,   Apoptosis↓, 1,   Apoptosis↑, 30,   BAD↓, 1,   BAD↑, 2,   Bak↑, 1,   BAX↑, 23,   Bax:Bcl2↑, 2,   Bcl-2↓, 24,   Bcl-xL↓, 5,   BID↑, 1,   Casp↓, 1,   Casp↑, 1,   Casp12↑, 1,   Casp3↓, 2,   Casp3↑, 18,   cl‑Casp3↑, 6,   proCasp3↓, 1,   Casp7↑, 3,   Casp8↑, 5,   cl‑Casp8↑, 1,   proCasp8↓, 1,   Casp9↓, 1,   Casp9↑, 18,   cl‑Casp9↑, 3,   proCasp9↓, 2,   CBP↓, 1,   Chk2↓, 1,   Chk2↑, 2,   Cyt‑c↓, 1,   Cyt‑c↑, 11,   DR5↑, 3,   FADD↑, 1,   Fas↑, 4,   FasL↑, 2,   HEY1↓, 1,   hTERT/TERT↓, 2,   IAP1↓, 1,   iNOS↓, 4,   JNK↓, 1,   JNK↑, 3,   p‑JNK↑, 2,   MAPK↓, 4,   MAPK↑, 3,   Mcl-1↓, 5,   MDM2↓, 5,   MOMP↑, 1,   NAIP↓, 1,   NICD↓, 1,   p27/CDKN1B↓, 1,   p27/CDKN1B↑, 7,   p38↑, 2,   p‑p38↑, 2,   survivin↓, 5,   Telomerase↓, 1,   TRAIL↑, 1,   TumCD↓, 1,   TumCD↑, 7,   YAP/TEAD↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

p‑cJun↑, 1,   EZH2↓, 1,   H3↑, 1,   ac‑H3↑, 1,   HATs↓, 1,   other↓, 1,   other↝, 1,   PhotoS↑, 2,   sonoS↑, 1,   tumCV↓, 5,  

Protein Folding & ER Stress(tgid=8) ⓘ

CHOP/DDIT3↑, 2,   eIF2α↑, 1,   ER Stress↓, 1,   ER Stress↑, 7,   GRP78/BiP↑, 1,   HSP90↓, 1,  

Autophagy & Lysosomes(tgid=9) ⓘ

Beclin-1↑, 1,   BNIP3↑, 1,   LC3‑Ⅱ/LC3‑Ⅰ↑, 1,   LC3B-II↑, 1,   LC3II↑, 1,   p62↑, 1,   TumAuto↑, 5,  

DNA Damage & Repair(tgid=10) ⓘ

ATM↑, 1,   CHK1↓, 2,   CHK1↑, 1,   DFF45↓, 1,   DNAdam↑, 5,   DNArepair↓, 1,   DNArepair↑, 1,   P53↓, 1,   P53↑, 22,   PARP↓, 2,   PARP↑, 4,   cl‑PARP↑, 10,   PCNA↓, 5,   PCNA↝, 1,   γH2AX↑, 2,  

Cell Cycle & Senescence(tgid=11) ⓘ

CDK1↓, 12,   CDK2↓, 14,   CDK4↓, 12,   Cyc↓, 1,   cycA1/CCNA1↓, 10,   cycA1/CCNA1↑, 2,   CycB/CCNB1↓, 50,   cycD1/CCND1↓, 15,   CycD3↓, 1,   cycE/CCNE↓, 3,   cycE1↓, 1,   E2Fs↓, 1,   P21↓, 1,   P21↑, 20,   RB1↑, 1,   p‑RB1↓, 1,   TumCCA↓, 3,   TumCCA↑, 40,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

cDC2↓, 3,   p‑cDC2↓, 1,   CSCs↓, 1,   EMT↓, 6,   EMT↑, 1,   ERK↓, 7,   p‑ERK↓, 4,   FGF↓, 1,   FOXO3↑, 1,   Gli1↓, 1,   GSK‐3β↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 2,   HDAC10↓, 1,   HH↓, 1,   IGF-1R↓, 1,   mTOR↓, 8,   p‑mTOR↓, 2,   mTORC2↓, 1,   NOTCH↓, 3,   NOTCH1↓, 1,   NOTCH1↑, 1,   p300↓, 1,   p‑P70S6K↓, 1,   p‑P90RSK↑, 1,   PI3K↓, 13,   p‑PI3K↓, 1,   PTEN↓, 1,   PTEN↑, 2,   RAS↓, 2,   Shh↓, 1,   Smo↓, 1,   STAT↓, 1,   STAT3↓, 12,   p‑STAT3↓, 1,   p‑STAT3↑, 1,   STAT5↓, 1,   TAZ↓, 1,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 10,   TumCG↑, 1,   Wnt↓, 1,   Wnt/(β-catenin)↓, 1,  

Migration(tgid=13) ⓘ

5LO↓, 1,   AEG1↓, 1,   AP-1↓, 2,   Ca+2↑, 3,   Cdc42↑, 1,   CDK4/6↓, 1,   E-cadherin↑, 6,   E-cadherin↝, 1,   ER-α36↓, 1,   FAK↓, 2,   p‑FAK↓, 2,   Ki-67↓, 2,   MMP1↓, 1,   MMP13↓, 2,   MMP2↓, 11,   MMP3↓, 2,   MMP7↓, 1,   MMP9↓, 12,   MMP9↑, 2,   MMPs↓, 3,   N-cadherin↓, 4,   N-cadherin↝, 1,   PKCδ↓, 2,   Rho↓, 2,   ROCK1↓, 3,   Slug↓, 3,   Snail↓, 4,   TGF-β↓, 1,   TIMP1↑, 3,   TIMP2↑, 3,   Treg lymp↓, 1,   TumCI↓, 9,   TumCMig↓, 7,   TumCP↓, 18,   TumCP↑, 1,   TumMeta↓, 8,   TumMeta↑, 1,   Twist↓, 2,   uPA↓, 4,   Vim↓, 3,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

angioG↓, 9,   ATF4↑, 2,   EGFR↓, 1,   p‑EGFR↓, 1,   Hif1a↓, 5,   NO↓, 1,   PDGFR-BB↓, 1,   VEGF↓, 12,   VEGFR2/KDR/Flk1↓, 2,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 2,   GLUT1↓, 1,   GLUT1↑, 1,   GLUT3↑, 1,   GLUT4↓, 1,   P-gp/ABCB1↓, 1,   P-gp/ABCB1∅, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

CD4+↓, 1,   CD4+↑, 1,   COX2/PTGS2↓, 11,   CXCR4↓, 2,   FOXP3↓, 1,   IFN-γ↓, 1,   IKKα↓, 1,   p‑IKKα↓, 1,   IL1↓, 3,   IL1α↓, 1,   IL1β↓, 2,   IL2↓, 2,   IL2↑, 1,   IL6↓, 5,   IL8↓, 3,   Imm↑, 2,   Inflam↓, 5,   Inflam↝, 1,   JAK2↓, 1,   MCP1/CCL2↓, 1,   mPGES-1↓, 1,   NF-kB↓, 16,   p‑NF-kB↑, 1,   NK cell↑, 1,   PD-L1↓, 2,   PGE2↓, 3,   T-Cell↑, 1,   Th1 response↑, 1,   TNF-α↓, 6,   TNF-α↑, 2,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

AR↓, 2,   RANKL↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 7,   BioAv↑, 6,   BioAv↝, 1,   ChemoSen↓, 1,   ChemoSen↑, 17,   Dose↝, 4,   Dose∅, 1,   eff↓, 8,   eff↑, 16,   eff↝, 1,   Half-Life↓, 3,   Half-Life↑, 1,   MDR1↓, 1,   RadioS↑, 6,   selectivity↑, 9,  

Clinical Biomarkers(tgid=22) ⓘ

AR↓, 2,   E6↓, 1,   E7↓, 1,   EGFR↓, 1,   p‑EGFR↓, 1,   EZH2↓, 1,   GutMicro↑, 1,   hTERT/TERT↓, 2,   IL6↓, 5,   Ki-67↓, 2,   PD-L1↓, 2,  

Functional Outcomes(tgid=23) ⓘ

AntiCan↑, 8,   AntiTum↑, 4,   cardioP↑, 2,   chemoP↑, 2,   chemoPv↑, 2,   ChemoSideEff↓, 1,   hepatoP↑, 1,   OS↑, 1,   radioP↑, 2,   RenoP↑, 2,   toxicity↓, 2,   TumVol↓, 5,   TumW↓, 2,  

Infection & Microbiome(tgid=24) ⓘ

Bacteria↓, 1,  
Total Targets: 342

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

diuretic↑, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

antiOx↓, 1,   antiOx↑, 10,   Catalase↑, 5,   GPx↑, 4,   GSH↑, 3,   GSR↑, 1,   GSTs↑, 3,   Keap1↓, 1,   lipid-P↓, 5,   MDA↓, 2,   MPO↓, 1,   NRF2↑, 2,   Prx↑, 1,   RNS↓, 1,   ROS↓, 12,   SOD↓, 1,   SOD↑, 5,   SOD2↑, 1,   TBARS↓, 1,  

Metal & Cofactor Biology(tgid=2) ⓘ

IronCh↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

MMP↑, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

ALAT↓, 1,   AMPK↑, 1,   glucose↓, 1,   H2S↑, 1,   LDH↓, 2,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,   Casp3?, 1,   cl‑Casp8↑, 1,   iNOS↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,  

DNA Damage & Repair(tgid=10) ⓘ

DNAdam↓, 1,   PARP↑, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

P21↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

PI3K↓, 1,   STAT3↓, 1,  

Migration(tgid=13) ⓘ

AntiAg↑, 1,  

Angiogenesis & Vasculature(tgid=14) ⓘ

NO↓, 2,  

Barriers & Transport(tgid=15) ⓘ

BBB↑, 2,   GastroP↑, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   IL6↓, 1,   Inflam↓, 7,   JAK↓, 1,   NF-kB↓, 2,   PGE2↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission(tgid=18) ⓘ

AChE↓, 2,   MAOA↓, 1,  

Protein Aggregation(tgid=19) ⓘ

AGEs↓, 1,   Aβ↓, 2,  

Drug Metabolism & Resistance(tgid=21) ⓘ

BioAv↓, 2,   BioAv↑, 5,   BioAv↝, 3,   eff↑, 2,   Half-Life↝, 2,  

Clinical Biomarkers(tgid=22) ⓘ

ALAT↓, 1,   AST↓, 1,   BP↓, 1,   creat↓, 1,   GutMicro↑, 1,   IL6↓, 1,   LDH↓, 2,  

Functional Outcomes(tgid=23) ⓘ

AntiDiabetic↑, 3,   AntiTum↓, 1,   cardioP↑, 2,   cognitive↑, 1,   hepatoP↑, 6,   memory↑, 1,   neuroP↑, 8,   Obesity↓, 1,   radioP↑, 1,   toxicity↓, 3,  

Infection & Microbiome(tgid=24) ⓘ

AntiViral↑, 1,   Bacteria↓, 2,  
Total Targets: 76

Scientific Paper Hit Count for: CycB/CCNB1, Cyclin B
8 Quercetin
4 Propolis -bee glue
3 Apigenin (mainly Parsley)
3 Eugenol
3 Cucurbitacin
3 Curcumin
3 Plumbagin
2 Allicin (mainly Garlic)
2 Baicalein
2 Betulinic acid
2 Chrysin
2 D-limonene
2 Emodin
2 Fenbendazole
2 Garcinol
2 Luteolin
2 Magnolol
2 Silymarin (Milk Thistle) silibinin
1 Phyllanthus emblica/Emblica officinalis/Amla / Indian Gooseberry
1 Andrographis
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Astaxanthin
1 Aloe anthraquinones
1 Berberine
1 Biochanin A
1 Bufalin/Huachansu
1 Cinnamon
1 Crocetin
1 Radiotherapy/Radiation
1 tamoxifen
1 Fisetin
1 Formononetin
1 Genistein (soy isoflavone)
1 isoflavones
1 isoorientin
1 Laetrile B17 Amygdalin
1 Lycopene
1 Melatonin
1 Magnetic Fields
1 Phenylbutyrate
1 Piperlongumine
1 Resveratrol
1 Sulforaphane (mainly Broccoli)
1 Vitexin
1 Isovitexin
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#:379  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

Home Page