Casp Cancer Research Results

Casp, caspase: Click to Expand ⟱
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The caspase family of proteases are essential to initiate and execute apoptotic cell death. Targeting caspase pathways by gene therapy or endogenous inhibitors represents a promising therapeutic strategy for cancer.
Caspases are divided into two groups: the initiator caspases (caspase-2, -8, -9 and -10), which are the first to be activated in response to a signal, and the executioner caspases (caspase-3, -6, and -7) that carry out the demolition phase of apoptosis.
Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases.
Scientific Papers found: Click to Expand⟱
5277- 3BP,    3-Bromopyruvate inhibits pancreatic tumor growth by stalling glycolysis, and dismantling mitochondria in a syngeneic mouse model
- in-vivo, PC, Panc02
HK2↓, It exerts potent anticancer effects by inhibiting hexokinase II enzyme (HK2) of the glycolytic pathway in cancer cells while not affecting the normal cells.
selectivity↑, it doesn’t affect the normal cells but strongly toxic to cancer cells
ATP↓, 3-BP killed 95% of Panc-2 cells at 15 μM concentration and severely inhibited ATP production by disrupting the interaction between HK2 and mitochondrial Voltage Dependent Anion Channel-1 (VDAC1) protein.
mtDam↑, Electron microscopy data revealed that 3-BP severely damaged mitochondrial membrane in cancer cells.
Dose↝, We further examined therapeutic effect of 3-BP in syngeneic mouse pancreatic cancer model by treating animals with 10, 15 and 20 mg/kg dose. 3-BP at 15 & 20 mg/kg dose level significantly reduced tumor growth by approximately 75-80% in C57BL/6 female
TumCG↓, 3-BP inhibit in vivo pancreatic tumor growth in C57BL/6 mouse model
Casp3↑, observed enhanced expression of active caspase-3 in tumor tissues exhibited apoptotic death.
Glycolysis↓, Notably, metabolomic data also revealed severe inhibition in glycolysis, NADP, ATP and lactic acid production in cancer cells treated with 40 μM 3-BP.
NADPH↓,
ATP↓,
ROS↑, 3-BP treatment produces increased levels of reactive oxygen species (ROS), which causes DNA damage with reduction of free glutathione levels [11].
DNAdam↑,
GSH↓,
Bcl-2↓, Further, treatment with 40 µM of 3-BP suppressed BCL2L1 expression and causing activation of mitochondrial caspases
Casp↑,
lactateProd↓, Metabolic inhibition of glucose consumption and lactic acid production in cancer cells treated with 3-BP

5434- AG,    Recent Advances in the Mechanisms and Applications of Astragalus Polysaccharides in Liver Cancer Treatment: An Overview
- Review, Liver, NA
AntiCan↑, Preclinical studies indicate that APS exerts significant anti-liver cancer effects through multiple biological actions, including the promotion of apoptosis, inhibition of proliferation, suppression of epithelial–mesenchymal transition, regulation of
Apoptosis↑,
TumCP↓,
EMT↓,
Imm↑, improving host immune response
ChemoSen↑, APS exhibits synergistic effects when combined with conventional chemotherapeutics and interventional treatments such as transarterial chemoembolisation, improving efficacy and reducing toxicity.
BioAv↓, limitations such as low bioavailability and a lack of large-scale clinical trials remain challenges for clinical translation.
TumCG↓, APS significantly inhibited tumour growth in H22-bearing mice with a dose-dependent effect (100, 200, 400 mg/kg), with the 400 mg/kg group achieving a tumour inhibition rate of 59.01%
IL2↑, APS enhance the thymus and spleen indices and elevates the key cytokines, including IL-2, IL-12, and TNF-α.
IL12↑,
TNF-α↑,
P-gp↓, APS reversed chemoresistance by downregulating P-glycoprotein and MDR1 mRNA expression
MDR1↓,
QoL↑, These effects contributed to improved treatment tolerance and enhanced quality of life [39].
Casp↑, APS can activate both the intrinsic and extrinsic apoptotic pathways, leading to caspase activation and DNA fragmentation
DNAdam↑,
Bcl-2↓, Mechanistically, APS downregulate antiapoptotic proteins such as Bcl-2 while upregulating proapoptotic proteins such as Bax and cleaved caspase-3.
BAX↑,
MMP↓, APS have been shown to disrupt the mitochondrial membrane potential and promote the release of cytochrome c, thereby enhancing apoptotic cascades in hepatocellular carcinoma models.
Cyt‑c↑,
NOTCH1↓, APS (0.1, 0.5, and 1.0 mg/mL) were shown to reduce both mRNA and protein levels of Notch1 in a concentration-dependent manner.
GSK‐3β↓, APS significantly inhibited the proliferation of HepG2 cells by downregulating the expression of glycogen synthase kinase-3β (GSK-3β), with 200 μg/mL being the most effective concentration.
TumCCA↑, APS exerted these effects by inducing cell cycle arrest at the G2/M and S phases, thereby impeding tumour cell proliferation [35].
GSH↓, HepG2 cells. APS also reduced intracellular glutathione (GSH) levels, increased reactive oxygen species (ROS) and lipid peroxidation levels, and elevated intracellular iron ion concentrations—all in a dose-dependent manner.
ROS↑,
lipid-P↑,
c-Iron↑,
GPx4↓, APS treatment led to the downregulation of GPX4 and upregulation of ACSL4, indicating that APS promotes ferroptosis in liver cancer cells.
ACSL4↑,
Ferroptosis↑,
Wnt↓, inhibit the expression of key proteins involved in the Wnt/β-catenin signalling pathway
β-catenin/ZEB1↓,
cycD1/CCND1↓, by downregulating the key oncogenic targets, including β-catenin, C-myc, and cyclin D1, which subsequently reduces Bcl-2 expression and activates the apoptotic cascade in HepG2 liver cancer cells.
Akt↓, It also inhibited the Akt/p-Akt signalling pathway.
PI3K↓, APS inhibit the PI3K/AKT/mTOR signalling pathway, which is a central negative regulator of autophagy.
mTOR↓,
CXCR4↓, PS upregulated the epithelial marker E-cadherin while downregulating the mesenchymal marker vimentin and the chemokine receptor CXCR4 at both mRNA and protein levels, suggesting that APS suppress liver cancer cell growth and metastasis by inhibiting
Vim↓,
PD-L1↓, APS interfere with immune checkpoint signalling by downregulating Programmed death-ligand 1 (PD-L1) expression on tumour cells.
eff↑, The preparation of polysaccharide–SeNP composites typically involves using sodium selenite (Na2SeO3) as the precursor and ascorbic acid (Vc) as the reducing agent, with synthesis carried out via a chemical reduction method in a polysaccharide solutio
eff↑, Mechanistic investigations revealed that AASP–SeNPs elevated intracellular ROS levels and reduced the mitochondrial membrane potential (∆Ψm).
ChemoSen↑, APS enhance doxorubicin-induced endoplasmic reticulum (ER) stress by reducing O-GlcNAcylation levels, thereby promoting apoptosis of liver cancer cells.
ChemoSen↑, APS inhibited BEL-7404 human liver cancer cell growth in a concentration-dependent manner and showed stronger cytotoxicity when combined with cisplatin.
chemoP↑, APS protects against chemotherapy-induced liver injury, particularly that caused by CTX, through antiapoptotic mechanisms

4403- AgNPs,    Silver Nanoparticles Decorated UiO-66-NH2 Metal-Organic Framework for Combination Therapy in Cancer Treatment
- in-vitro, GBM, U251 - in-vitro, GBM, U87MG - in-vitro, GBM, GL26 - in-vitro, Cerv, HeLa - in-vitro, CRC, RKO
AntiCan↑, Among the various NPs, silver nanoparticles (AgNPs) have garnered attention due to their cytotoxic and genotoxic properties in cancer cells.
eff↑, Our results demonstrate that UiO-66-NH2@AgNPs@Cis-Pt and its combinations exhibit enhanced cytotoxicity compared to individual components such as AgNPs and Cis-Pt.
EPR↑, Their nanometric structure allows them to easily penetrate and accumulate in tumour tissues either actively, via targeting systems [6,7,8], or passively, by taking advantage of tumour angiogenesis and the enhanced permeation and retention (EPR) effe
selectivity↑,
ROS↑, Once inside, AgNPs induce an increase in the production of reactive oxygen species (ROS) and cause mitochondrial dysfunctions, caspases activation, apoptosis, autophagy, and DNA damage
Casp↑,
Apoptosis↑,
DNAdam↑,
tumCV↓, figure 8
eff↑, One of the primary characteristics of AgNPs is their ability to release Ag+ ions from their surface in response to low pH or oxidation.

5142- AgNPs,    Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells
- in-vitro, CRC, HUH7
ROS↑, Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis.
Apoptosis↑,
eff↑, Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death
ChemoSen↑, bAgNPs Enhance Cytotoxicity of Chemotherapeutic Drug Cisplatin (CDDP)
EPR↑, The AgNPs were selected over free metal silver for exploration of their anticancerous effects because of the enhanced permeability of NPs into tumors, attributable to the EPR effect.
Casp↑, Induction of Apoptotic Cell Death by bAgNPs through Activation of Caspases
MAPK↑, Our results provide strong evidence for selective activation of MAPK pathways following AgNP exposure

361- AgNPs,    Annona muricata assisted biogenic synthesis of silver nanoparticles regulates cell cycle arrest in NSCLC cell lines
- in-vitro, Lung, A549
Apoptosis↑,
Casp↑,
TumCCA↑,

388- AgNPs,    Apoptotic efficacy of multifaceted biosynthesized silver nanoparticles on human adenocarcinoma cells
- in-vitro, BC, MCF-7
ROS↑, ROS production
Casp3↑,
BAX↑,
P53↑,
Casp↑, Upregulation of caspases, apoptotic mediators, were observed after exposure of MCF-7 to the RAgNPs
Cyt‑c↑, The release of cytochrome c was determined after 24 h RAgNPs treatment.
MMP↓, The treated cells increased the depolarized mitochondrial membrane and decreased the polarized membranes.
DNAdam↑, Ag NPs perform well as cancer therapeutics because they can disrupt the mitochondrial respiratory chain, which induces the ROS generation, DNA damage and ATP synthesis
Bcl-2↓, Upon treatment with AgNPs or cisplatin, MCF-7 cells showed decreased Bcl-2 expression and increased Bax expression, representing the mitochondrial connection in cell death
BAX↑,

5356- AL,    Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects
- Review, GC, NA
Apoptosis↑, induction of apoptosis, inhibition of proliferation, and disruption of cancer cell signaling pathways, including the MAPK, PI3K/AKT, and NF-κB pathways.
TumCP↓,
MAPK↓,
PI3K↓,
Akt↓,
NF-kB↓,
AntiCan↑, Allicin and its other derivatives, such as diallyl disulfide (DADS) and ajoene, have been found to have strong anticancer potential both in vitro and in vivo.
ChemoSen↑, effectiveness of allicin in augmenting conventional chemotherapy and retarding tumor growth proves that allicin is one of the most efficient complementary therapies.
TumCCA↑, In liver cancer, allicin has been shown to mediate cell cycle arrest and apoptosis
Apoptosis↑,
BioAv↑, Allicin (diallyl thiosulfinate) is a compound that is generated when a garlic clove is crushed
selectivity↑, Furthermore, it has no influence on the growth of healthy intestinal cells when it causes stomach cancer cells to undergo apoptosis
TGF-β↓, Allicin can reduce the production of TGF-β2 and its receptor after directly entering gastric cancer cells.
ROS↑, It induces oxidative stress by generating reactive oxygen species (ROS), leading to DNA damage and activation of key apoptotic mediators such as phospho-p53 and p21 [81].
DNAdam↑,
p‑P53↑,
P21↑,
cycD1/CCND1↓, Additionally, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs) can all be inhibited by allicin.
cycE/CCNE↓,
CDK4↓, suppressing the CDK-4/6/cyclin D complex
CDK6↓,
MMP↓, By lowering the outer mitochondrial membrane potential (MMP), allicin raises levels of nuclear factor kappa B (NF-κB), the proapoptotic protein Bax, while decreasing the antiapoptotic protein Bcl-2, which leads to apoptosis.
NF-kB↑,
BAX↑,
Bcl-2↓,
ER Stress↑, cellular effects of allicin, including its role in inducing ER stress
Casp↑, enhancing caspase activation and apoptosis-inducing factor (AIF)-mediated cell death.
AIF↑,
Fas↑, increasing Fas receptor expression and its binding to Fas ligand (FasL), leading to apoptosis through caspase-8 and cytochrome c activation.
Casp8↑,
Cyt‑c↑,
cl‑PARP↑, leading to poly (ADP-ribose) polymerase (PARP) cleavage and DNA fragmentation.
Ca+2↑, allicin elevates intracellular free Ca2⁺ levels, causing endoplasmic reticulum (ER) stress, which plays a critical role in apoptosis induction
*NRF2↑, by activating the Nrf2 pathway via KLF9, allicin protects against arsenic trioxide-induced liver damage,
*chemoP↑, Additionally, allicin has shown promise in reducing hepatotoxicity caused by tamoxifen (TAM), a commonly used treatment for hormone-dependent breast cancer
*GutMicro↑, Shi et al. [85] found that allicin can ameliorate high-fat diet-induced obesity in mice by altering their gut microbiome.
CycB/CCNB1↑, DATS impaired cell survival in the G2 phase by significantly upregulating cyclins A2 and B1.
H2S↑, DATS can also react with the cellular thiol glutathione to create H2S gas, which can control several other cellular functions [79].
HIF-1↓, allicin treatment (40 µg/ml) for NSCLC lowers the expression of HIF-1 and HIF-2 in hypoxic cells [73]
RadioS↑, Allicin has been shown to increase the sensitivity of X-ray radiation therapy in colorectal cancer, presumably by suppressing the levels of NF-κB, IKKβ mRNA, p-NF-κB, and p-IKKβ protein expression in vitro and in vivo

2647- AL,    The Mechanism in Gastric Cancer Chemoprevention by Allicin
- Review, GC, NA
ChemoSen↓, Experiments have shown that allicin can be chemopreventive to gastric cancer
TumCG↓, by inhibiting the growth of cancer cells, arresting cell cycle at G2/M phase, endoplasmic reticulum (ER) stress, and mitochondria-mediated apoptosis, which includes the caspase-dependent/-independent pathways and death receptor pathway.
TumCCA↑,
ER Stress↑,
Apoptosis↑,
Casp↑,
DR5↑, DR5 (death receptor 5) was found to be upregulated following allicin treatment

2658- AL,    The Toxic Effect Ways of Allicin on Different Cell Lines
- Review, Var, NA
*antiOx↑, The significant functional act of garlic is its anticancer, antimicrobial, antioxidant, antidiabetic, antifibrinolytic, immune enhancing, antiplatelet collected effect and its possible act in prohibiting cardiovascular illnesses
*AntiAg↑,
*cardioP↑,
Ca+2↑, Sultan et al.[34] stated that allicin is cytotoxic to monocytic leukemia cells (THP-1 cells) and stimulates calcium-linked hemolysis and eryptosis in human red blood cells. Allicin advances calcium grades in cells, reasons to oxidative stress and al
ROS↑, Allicin advances calcium grades in cells, reasons to oxidative stress and also induces CK1a, caspase, p38, mitogen-activated protein kinase
Casp↑,
p38↑,
MAPK↑,
hepatoP↑, Wu et al.[42] clarified that allicin applies hepaprotective action counter to hepatic toxicity of cells
chemoP↑, Throughout with other garlic preparations, aged garlic extract (AGE) has been indicated to have hepatoprotective, immune, improving, anticancer, and chemoprotective actions.

3442- ALA,    α‑lipoic acid modulates prostate cancer cell growth and bone cell differentiation
- in-vitro, Pca, 22Rv1 - in-vitro, Pca, C4-2B - in-vitro, Nor, 3T3
tumCV↓, Notably, α‑LA treatment significantly reduced the cell viability, migration, and invasion of PCa cell lines in a dose‑dependent manner.
TumCMig↓,
TumCI↓,
ROS↑, α‑LA supplementation dramatically increased reactive oxygen species (ROS) levels and HIF‑1α expression, which started the downstream molecular cascade and activated JNK/caspase‑3 signaling pathway
Hif1a↑, The expression of HIF-1α significantly increased following α-LA treatment and was comparable with the changes in ROS.
JNK↑,
Casp↑,
TumCCA↑, arrest of the cell cycle in the S‑phase, which has led to apoptosis of PCa cells
Apoptosis↑,
selectivity↑, Also, the treatment of α‑LA improved bone health by reducing PCa‑mediated bone cell modulation.

282- ALA,    Alpha-lipoic acid induced apoptosis of PC3 prostate cancer cells through an alteration on mitochondrial membrane depolarization and MMP-9 mRNA expression
- in-vitro, Pca, PC3
MMP↓, significant alteration
Casp↑,
MMP9↓, at the mRNA level

259- ALA,    Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells
- in-vitro, Liver, HepG2 - in-vitro, Liver, FaO
Cyc↓, cyclin A
P21↑,
ROS↑, α-LA treatment at a concentration that induces apoptosis (500 µM) caused increased ROS generation in FaO cells, as early as 1 h after treatment with a further increase at 3 and 6 h.
p‑P53↑,
BAX↑, 500 µM α-LA produced an increase in Bax levels as early as 24 h
Cyt‑c↑, release from mitochondria
Casp↑, Treatment of HepG2 cells with 500 µM α-LA caused a time-dependent activation of caspase-3, as indicated by a progressive decrease of levels of pro-caspase-3
survivin↓,
JNK↑,
Akt↓,

1253- aLinA,    The Antitumor Effects of α-Linolenic Acid
- Review, NA, NA
PPARγ↑,
COX2↓,
E6↓,
E7↓,
P53↑,
p‑ERK↓,
p38↓,
lipid-P↑,
ROS⇅, ALA could inhibit cancer by stimulating ROS production to induce apoptosis (other places implies reduced) appropriate dose of ALA can also reduce OS by regulating SOD, CAT, GPx, GSH, and NADPH oxidase
MPT↑, directly activate mitochondrial permeability transition
MMP↓,
Cyt‑c↑, cytochrome c (cyt c) release
Casp↑,
iNOS↓,
NO↓,
Casp3↑,
Bcl-2↓,
Hif1a↓,
FASN↓,
CRP↓,
IL6↓,
IL1β↓,
IFN-γ↓,
TNF-α↓,
Twist↓,
VEGF↓,
MMP2↓,
MMP9↓,

1564- Api,    Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation
- in-vitro, Pca, 22Rv1 - in-vivo, NA, NA
MDM2↓, downregulation of MDM2 protein
NF-kB↓, Exposure of 22Rv1 cells to 20 μM apigenin caused a decrease in NF-κB/p65 transcriptional activity by 24% at 12 h, which was further decreased to 41% at 24 h
p65↓,
P21↑,
ROS↑, Apigenin at these doses resulted in ROS generation
GSH↓, which was accompanied by rapid glutathione depletion
MMP↓, disruption of mitochondrial membrane potential
Cyt‑c↑, cytosolic release of cytochrome c
Apoptosis↑,
P53↑, accumulation of a p53 fraction to the mitochondria, which was rapid and occurred between 1 and 3 h after apigenin treatment
eff↓, All these effects were significantly blocked by pretreatment of cells with the antioxidant N-acetylcysteine
Bcl-xL↓,
Bcl-2↓,
BAX↑,
Casp↑, triggering caspase activation
TumCG↓, in vivo mice
TumVol↓, tumor volume was inhibited by 44 and 59%
TumW↓, wet weight of tumor was decreased by 41 and 53%

2632- Api,    Apigenin inhibits migration and induces apoptosis of human endometrial carcinoma Ishikawa cells via PI3K-AKT-GSK-3β pathway and endoplasmic reticulum stress
- in-vitro, EC, NA
TumCP↓, We found that API could inhibit the proliferation of Ishikawa cells at IC50 of 45.55 μM, arrest the cell cycle at G2/M phase, induce apoptosis by inhibiting Bcl-xl and increasing Bax, Bak and Caspases.
TumCCA↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
Bak↑,
Casp↑,
ER Stress↑, Further, API could induce apoptosis by activating the endoplasmic reticulum (ER) stress pathway by increasing the Ca2+, ATF4, and CHOP.
Ca+2↑, after API treatment for 48 h, the intracellular Ca2+ concentration increased in cells in a dose-dependent manner.
ATF4↑,
CHOP↑,
ROS↑, the level of intracellular ROS increased gradually with the increase of API concentration.
MMP↓, mitochondrial membrane potential of 30 μM, 50 μM, and 70 μM groups decreased by 2.19%, 11.32%, and 14.91%, respectively.
TumCMig↓, API inhibits the migration and invasion of Ishikawa cells and the migration and invasion related gene and protein.
TumCI↓,
eff↑, In our study, API restrained the viability of Ishikawa cells, and the inhibition effect of API on Ishikawa cells was better than that of 5-FU.
P53↑, API induces p53 tumor suppressor proteins at the translational level and the induces p21
P21↑,
Cyt‑c↑, After the mitochondria release the Cyto-c, the Caspase-9 is activated, resulting in increased activity of Caspases
Casp9↑, In our study, the expression levels of Bad, Bax, Cyto-c, Caspase-9 and Caspase-3 proteins were up-regulated,
Casp3↑,
Bcl-xL↓, while the expression level of Bcl-xl was down-regulated

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

5129- ART/DHA,    Evidence for the Involvement of Carbon-centered Radicals in the Induction of Apoptotic Cell Death by Artemisinin Compounds
- in-vitro, AML, HL-60
Casp↑, In HL-60 cells the endoperoxides induce caspase-dependent apoptotic cell death characterized by concentration- and time-dependent mitochondrial membrane depolarization, activation of caspases-3 and -7, sub-G0/G1 DNA formation
Apoptosis↑,
MMP↓,
TumCCA↑,
eff↑, have led the World Health Organization to recommend the use of ART-based combination therapies to all countries experiencing resistance to conventional monotherapies.
eff↑, The most sensitive cell lines are characterized by their rapid proliferation, often accompanied by a high intracellular iron concentration to sustain continued proliferation

5396- Ash,    Withania Somnifera (Ashwagandha) and Withaferin A: Potential in Integrative Oncology
- Review, Var, NA
selectivity↑, WS was shown to impede the growth of new cancer cells, but not normal cells,
ROS↑, help induce programmed death of cells by generating reactive oxygen species (ROS), and sensistize cancer cells to apoptosis
Apoptosis↑,
ChemoSen↑, Pre-clinical studies in several cancer types have shown up to 80% inhibition using combination chemotherapy [19].
RadioS↑, It was not until 1996, that WFA’s radiosensitizer activity was reported that caused V79 cell survival reduction where 1-h pre-treatment at 2.1 µM dose before radiation significantly killed cells
NF-kB↓, inhibiting NF-κB activation
ER-α36↓, WFA, it was found the phytochemical downregulated the estrogen receptor-α (ER-α) protein in MCF-7 cells.
P53↑, WFA selectively activated p53 in tumor cells treated with the leaf extract of Ashwagandha [71] leading to growth arrest and apoptosis.
*ROS∅, opposed to the normal human mammary epithelial cells (HMEC) [72] which did not increase ROS production.
γH2AX↑, The group found an increase in γ-H2AX and number of cells expressing the phosphorylated form which is a marker for DNA damage in WFA treated MCF-7 cells.
DNAdam↑,
MMP↓, As ROS is well known to affect mithochondrial membrane potential, they found a change in mitochondrial membrane potential and altered mitochondrial morphology in WFA treated cells.
XIAP↓, XIAP (X-linked inhibitor of apoptosis protein), cIAP-2 (cellular inhibitor of apoptosis protein-2) and Survivin proteins were found to be reduced in MDA-MB-231 and MCF-7 cells when treated with WFA
IAP1↓,
survivin↓,
SOD↓, figure 2
Dose↝, doses of 3 and 4 mg/kg and the authors found 59% reduction of tumor and polyp initiation and progression in the WFA treated mice compared to the controls [80].
IL6↓, WFA downregulated expression of inflammatory markers in these tumors such as IL-6, TNF-α, COX-2 along with pro-survival markers such as pAkt, Notch1 and NF-κβ [80].
TNF-α↓,
COX2↓,
p‑Akt↓,
NOTCH1↓,
FOXO↑, figure 3 prostrate cancer
Casp↑,
MMP2↓,
CSCs↓, WFA treatment significantly reduced ALDH+ CSC population, whereas Cisplatin treatment increased CSC population.
*ROS↓, WFA was found to increase cellular survival in simulated injury and in H2O2-induced cell apoptosis along with inhibition of oxidative stress.
*SOD2↑, Thus, via upregulation of SOD2, SOD3, Prdx-1 by H2O2, WFA treatment leads to inhibition of the antioxidants and Akt-dependent improvement of cardiomyocyte caspase-3 [103].
chemoP↑, First, given the safety record of WS, it can be used as an adjunct therapy that can aid in reducing the adverse effects associated with radio and chemotherapy due to its anti-inflammatory properties.
ChemoSen↑, Second, WS can also be combined with other conventional therapies such as chemotherapies to synergize and potentiate the effects due to radiotherapy and chemotherapy due to its ability to aid in radio- and chemosensitization, respectively.
RadioS↑,

5449- ATV,    Pleiotropic effects of statins: A focus on cancer
- NA, Var, NA
lipid-P↓, Statins exhibit “pleiotropic” properties that are independent of their lipid-lowering effects.
TumCG↓, preclinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types.
Apoptosis↑,
ChemoSen↑, statins show chemo-sensitizing effects by impairing Ras family GTPase signaling.
RAS↓,
HMG-CoA↓, Statins are potent, competitive inhibitors of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR).
HMGCR↓,
LDL↓, Statins reduce blood plasma cholesterol levels by decreasing de novo cholesterol biosynthesis and by inducing changes in low density lipoprotein (LDL) receptor expression [2].
toxicity↓, Due to the well-established safety profile of statins, such studies are less expensive than the development of novel drugs.
Risk↓, statin use in cancer patients was associated with reduced cancer-related mortality. The risk of cancer death was significantly lower in postmenopausal women
P21↑, Other proposed mechanisms leading to an increase of p21 levels include the release of promoter-associated histone deacetylase and inhibition of histone deacetylase
HDAC↓,
Bcl-2↓, Statins trigger the intrinsic apoptosis pathway and decrease Bcl-2 protein expression [[154], [155], [156]], increase Bax and BIM protein expression [[156], [157], [158], [159]], and activate several caspases
BAX↑,
BIM↑,
Casp↑,
cl‑PARP↑, thereby increasing cleaved PARP-1 levels.
MMP↓, different tumor cell lines (breast, brain, and lung) showed that simvastatin-induced apoptosis is dependent on decreasing mitochondrial membrane potential and increasing reactive oxygen species (ROS) production
ROS↑,
angioG↓, Statins inhibit angiogenesis and metastasis
TumMeta↓,
PTEN↑, n breast cancer xenografts, simvastatin prevented tumor growth by reducing Akt phosphorylation and BclXL transcription, while simultaneously increasing the transcription of pro-apoptotic/anti-proliferative PTEN
eff↑, In mice, the administration of a combination of celecoxib and atorvastatin was more effective than each individual treatment, and effectively prevented prostate cancer progression from androgen dependent to androgen independent
OS↑, Long-term statin use may improve survival in GBM patients treated with temozolomide chemotherapy
Remission↑, statin use during or after chemotherapy is not associated with improved disease-free-, recurrence-free-, or overall survival in stage II colon cancer patients

2699- BBR,    Plant Isoquinoline Alkaloid Berberine Exhibits Chromatin Remodeling by Modulation of Histone Deacetylase To Induce Growth Arrest and Apoptosis in the A549 Cell Line
- in-vitro, Lung, A549
HDAC↓, BBR represses total HDAC and also class I, II, and IV HDAC activity through hyperacetylation of histones.
TumCCA↑, BBR triggers positive regulation of the sub-G0/G1 cell cycle progression phase in A549 cells.
TNF-α↓, BBR downregulates oncogenes (TNF-α, COX-2, MMP-2, and MMP-9) and upregulates tumor suppressor genes (p21 and p53) mRNA and protein expressions.
COX2↓,
MMP2↓, BBR Induces Downregulation of MMP-2 and MMP-9
MMP9↓,
P21↑,
P53↑,
Casp↑, triggered the caspase cascade apoptotic pathway in A549 cells
ac‑H3↑, BBR Increases the Acetylation State of Histones H3 and H4.
ac‑H4↑,
ROS↑, BBR Induces ROS Generation, Δψm Alteration, Membrane Loss, and Nuclear Fragmentation
MMP↓,

5180- BBR,    Berberine Targets AP-2/hTERT, NF-κB/COX-2, HIF-1α/VEGF and Cytochrome-c/Caspase Signaling to Suppress Human Cancer Cell Growth
- in-vitro, NSCLC, NA
TumCMig↓, BBR promoted cell morphology change, inhibited cell migration, proliferation and colony formation, and induced cell apoptosis.
TumCP↓,
Apoptosis↑,
TFAP2A↓, BBR inhibited AP-2α and AP-2β expression and abrogated their binding on hTERT promoters, thereby inhibiting hTERT expression.
hTERT/TERT↓,
NF-kB↓, BBR also suppressed the nuclear translocation of p50/p65 NF-κB proteins and their binding to COX-2 promoter, causing inhibition of COX-2.
COX2↓,
Hif1a↓, BBR also downregulated HIF-1α and VEGF expression and inhibited Akt and ERK phosphorylation.
VEGF↓,
Akt↓,
p‑ERK↓,
Cyt‑c↑, BBR treatment triggered cytochrome-c release from mitochondrial inter-membrane space into cytosol, promoted cleavage of caspase and PARP,
cl‑Casp↑,
cl‑PARP↑,
PI3K↓, BBR inhibited HIF-1α/VEGF, PI3K/AKT, Raf/MEK/ERK signaling
Akt↓,
Raf↓,
MEK↓,
ERK↓,

5584- BetA,    Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors
- in-vitro, GBM, A172 - in-vitro, GBM, U118MG - in-vitro, GBM, U251
Apoptosis↑, BetA induced apoptosis by a direct effect on mitochondria independent of accumulation of wild-type p53 protein and independent of death-inducing ligand/receptor systems such as CD95.
P53↑,
Cyt‑c↑, release of soluble apoptogenic factors such as cytochrome c or AIF from mitochondria into the cytosol, where they induced activation of caspases.
AIF↑,
Casp↑,
AntiTum↑, BetA exhibited potent antitumor activity on neuroblastoma cells resistant to CD95- or doxorubicin-triggered apoptosis and on primary tumor cells from patients with neuroectodermal tumors.
MMP↓, BetA resulted in loss of the mitochondrial membrane potential

2730- BetA,    Betulinic acid induces autophagy-dependent apoptosis via Bmi-1/ROS/AMPK-mTOR-ULK1 axis in human bladder cancer cells
- in-vitro, Bladder, T24/HTB-9
tumCV↓, The present study showed that BA exposure significantly suppressed viability, proliferation, and migration of EJ and T24 human bladder cancer cells
TumCP↓,
TumCMig↓,
Casp↑, These effects reflected caspase 3-mediated apoptosis
TumAuto↑, BA-induced autophagy was evidenced by epifluorescence imaging of lentivirus-induced expression of mCherry-GFP-LC3B and increased expression of two autophagy-related proteins, LC3B-II and TEM.
LC3B-II↑,
p‑AMPK↑, Moreover, enhanced AMPK phosphorylation and decreased mTOR and ULK-1 phosphorylation suggested BA activates autophagy via the AMPK/mTOR/ULK1 pathway.
mTOR↓,
BMI1↓, decreased Bmi-1 expression in BA-treated T24 cell xenografts in nude mice suggested that downregulation of Bmi-1 is the underlying mechanism in BA-mediated, autophagy-dependent apoptosis.
ROS↑, BA induced ROS production dose-dependently
eff↓, Co-incubation with NAC effectively blocked ROS production (Figure 4B), rescued cell viability,

2735- BetA,    Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications
- Review, Var, NA
mt-Apoptosis↑, BA and analogues (BAs) have been known to exhibit potential antitumor action via provoking the mitochondrial pathway of apoptosis
Casp↑, cytosolic caspase activation
p38↑, inhibition of pro-apoptotic p38, MAPK and SAP/JNK kinases [8],
MAPK↓,
JNK↓,
VEGF↓, decreased expression of pro-apoptotic proteins and vascular endothelial growth factor (VEGF)
AIF↑, BA was recognized to trigger the process of apoptosis in human metastatic melanoma cells (Me-45) by releasing apoptosis inducing factor (AIF) and cytochrome c (Cyt C) through mitochondrial membrane
Cyt‑c↑,
ROS↑, BA also stimulates the increased production of reactive oxygen species (ROS) that is considered a stress factor involved in initiating mitochondrial membrane permeabilization
Ca+2↑, Moreover, the calcium overload and thereby ATP depletion are other stress factors causing enhanced inner mitochondrial membrane permeability via nonspecific pores formation
ATP↓,
NF-kB↓, BA has also known to be involved in activation of nuclear factor kappa B (NF-κB) that is responsible for apoptosis induction in variety of cancer cells
ATF3↓, According to Zhang et al. [14], BA stimulates apoptosis through the suppression of cyclic AMP-dependent transcription factor ATF-3 and NF-κB pathways and downregulation of p53 gene.
TOP1↓, inhibition of topoisomerases
VEGF↓, ecreased expression of vascular endothelial growth (VEGF) and the anti-apoptotic protein surviving in LNCaP prostate cancer cells.
survivin↓,
Sp1/3/4↓, selective proteasome-dependent targeted degradation of transcription factors specificity proteins (Sp1, Sp3, and Sp4), which generally regulate VEGF and survivin expression and highly over-expressed in tumor conditions
MMP↓, perturbed mitochondrial membrane potential
ChemoSen↑, BA can support as sensitizer in combination therapy to enhance the anticancer effects with minimum side effects.
selectivity↑, Normal human fibroblasts [41], peripheral blood lymphoblasts [41], melanocytes [32] and astrocytes [30] were found to be resistant to BA in vitro
BioAv↓, The clinical use of BA is seriously challenging due to high hydrophobicity which subsequently causes poor bioavailability
BioAv↑, A BA-loaded oil-in-water nanoemulsion was developed using phospholipase-catalyzed modified phosphatidylcholine as emulsifier in an ultrasonicator [120].
BioAv↑, Aqueous solubility of BA may also be increased through grinding with hydrophilic polymers (polyethylene glycol, polyvinylpyrrolidone, arabinogalactan) [121,122].
BioAv↑, Subsequently, for further improvement in biocompatibility, a technique of nanotube coating was employed with four biopolymers i.e. polyethylene glycol (PEG), chitosan, tween 20 and tween 80.
BioAv↑, Similarly, BA-coated silver nanoparticles displayed an improved antiproliferative and antimigratory activity, particularly against melanoma cells (A375: murine melanoma cells)

2743- BetA,    Betulinic acid and the pharmacological effects of tumor suppression
- Review, Var, NA
ROS↑, BA improves the level of reactive oxygen species (ROS) production and alters the mitochondrial membrane potential gradient, followed by the release of cytochrome c (Cyt c), which causes the mitochondrial-mediated apoptosis of tumor cells via a caspas
MMP↓,
Cyt‑c↑,
Apoptosis↑,
TumCCA↑, BA can inhibit cancer cell growth and proliferation via cell cycle arrest
Sp1/3/4↓, BA, can inhibit the protein expression of Sp1, Sp2 and Sp4 through the microRNA (miR)-27a-ZBTB10-Sp1 axis
STAT3↓, BA can downregulate the activation of STAT3 through the upregulation of Src homology 2 domain-containing phosphatase 1 (SHP-1)
NF-kB↓, NF-κB can be inhibited by reducing the activation of inhibitor of NF-κB (IκBα) kinase (IKKβ) and phosphorylation of IκBα with BA
EMT↓, nvasion and metastasis of malignancies is prevented via epithelial-mesenchymal transition (EMT) and inhibition of topoisomerase I
TOP1↓,
MAPK↑, BA leads to the activation, via phosphorylation, of pro-apoptotic MAPK proteins, P38 and SAP/JNK, the formation of ROS and the upregulation of caspase
p38↑,
JNK↑,
Casp↑,
Bcl-2↓, BA downregulates Bcl-2 and upregulates the Bax gene in HeLa cell lines
BAX↑,
VEGF↓, BA can decrease the expression of VEGF via Sp proteins, thus having an antiangiogenic role
LAMs↓, BA suppresses the expression of lamin B1 in pancreatic cancer cells

2748- BetA,    Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy
- Review, Var, NA
Bcl-2↓, Cell death stimuli activate prodeath BCL-2 family proteins that in turn permeabilize mitochondrial outer membrane, thereby resulting in the release of Cyt C
MMP↓,
Cyt‑c↑,
Casp↑, Smac (second mitochondria-derived activator of caspase)/DIABLO (direct inhibitor of apoptosis [IAP] binding protein with low pI), and AIF (apoptosis-inducing factor) into the cytoplasm (27
Diablo↑,
AIF↑,
angioG↓, BetA's inhibition of growth-factor-induced angiogenesis seems at least partially owing to modulation of mitochondrial function in endothelial cells
BioAv↓, Current methods of conventional drug delivery using oral liquids or tablets are generally inefficient, with poor biodis- tribution, low solubility, long-term toxicity, and limited drug efficacy due to partial biodegradation, swelling, and ero- sion
NF-kB↓, BetA treatment inhibits the activation of NF-kB

2754- BetA,    Betulinic acid inhibits prostate cancer growth through inhibition of specificity protein transcription factors
- in-vitro, Pca, LNCaP
VEGF↓, betulinic acid decreases expression of vascular endothelial growth (VEGF)
survivin↓, and the antiapoptotic protein survivin
Sp1/3/4↓, betulinic acid acts as a novel anticancer agent through targeted degradation of Sp proteins that are highly overexpressed in tumors.
Casp↑, Betulinic acid also induced caspase-dependent PARP cleavage in LNCaP cells, and this was accompanied by decreased expression of the antiapoptotic protein survivin
PARP↑,
survivin↓,
angioG↓, betulinic acid also induces proapoptotic and antiangiogenic responses in LNCaP cells as evidenced by decreased expression of VEGF and survivin and activation of caspase-dependent PARP cleavage

5721- BF,    Bufalin Suppresses Triple-Negative Breast Cancer Stem Cell Growth by Inhibiting the Wnt/β-Catenin Signaling Pathway
- in-vitro, BC, NA
CSCs↓, Bufalin effectively suppressed TNBCSC self-renewal in in vitro tumorsphere assays and significantly reduced tumor growth in an in vivo HCC1937 TNBCSC xenograft chorioallantoic membrane (CAM) model.
TumCCA↑, Bufalin induced G0/G1 phase cell cycle arrest by downregulating key regulatory proteins, including c-myc, cyclin D1, and CDK4.
cMyc↓,
cycD1/CCND1↓,
CDK4↓,
MMP↓, It also promoted intrinsic apoptosis through nuclear fragmentation, mitochondrial membrane potential reduction, and caspase activation.
Casp↑,
CD133↓, bufalin downregulated key CSC markers, such as CD133, CD44, ALDH1A1, Nanog, Oct4, and Sox2.
CD44↓,
ALDH1A1↓,
Nanog↓,
OCT4↓,
SOX2↓,
Wnt↓, Notably, bufalin suppressed the Wnt/β-catenin signaling pathway by reducing β-catenin mRNA and protein expression, leading to the downregulation of EGFR, a downstream target of Wnt signaling.
β-catenin/ZEB1↓,
EGFR↓,

5690- BJ,  BRU,    Brusatol: A potential sensitizing agent for cancer therapy from Brucea javanica
- Review, Var, NA
NRF2↓, Brusatol is a potent Nrf2 inhibitor for future cancer treatment.
TumCG↓, Brusatol exhibits significant tumor inhibition in multiple cancers.
ChemoSen↑, also exhibits significant synergistic antitumor effects in combination with chemotherapeutic agents
ROS↑, Graphical Abstract
NF-kB↓,
Akt↓,
mTOR↓,
TumCCA↑,
Apoptosis↑,
PARP↑,
Casp↑,
P53↓,
Bcl-2↓,
PI3K↓,
JAK2↓,
EMT↓,
p27↑,
ROCK1↓,
MMP2↓,
MMP9↓,
NRF2↓, which is the reason why brusatol is called an Nrf2 inhibitor [15]. Brusatol is a potent Nrf2 inhibitor
AntiTum↑, Brusatol shows significant antitumor effects in vitro and in vivo
HO-1↓, Moreover, brusatol inhibited the expression of Nrf2 downstream genes, such as HO-1 [19], [31], [32], NQO1 [43], [44], VEGF [45], and AKR1C1 [46].
NQO1↓,
VEGF↓,
MRP1↓, brusatol reduced both the mRNA and protein levels of NQO1, HO-1, MDR1, and MRP5
RadioS↑, Improvement of sensitivity to radiotherapy and phototherapy
PhotoS↑,
toxicity↝, the toxicity of brusatol is a problem that can not be ignored.

5658- BNL,    Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage
- vitro+vivo, GBM, U251
ChemoSen↑, combined treatment of NB and TMZ more effectively inhibited human glioma growth via triggering mitochondria-mediated apoptosis in vitro, accompanied by the caspase activation.
mt-Apoptosis↑,
Casp↑,
DNAdam↑, NB enhanced TMZ-induced DNA damage through inducing reactive oxide species (ROS) overproduction.
ROS↑,
angioG↓, anti-angiogenesis.
BBB↑, It is reported that NB could improve the oral bioavailability of anti-tumor drugs by regulating the permeability of the BBB.
EPR↑,
TumVol↓, combined treatment of NB and TMZ significantly inhibited tumor volume and tumor weight compared to that in treatment with NB or TMZ alone
TumW↓,
BioEnh↑,

2775- Bos,    The journey of boswellic acids from synthesis to pharmacological activities
- Review, Var, NA - Review, AD, NA - Review, PSA, NA
ROS↑, modulation of reactive oxygen species (ROS) formation and the resulting endoplasmic reticulum stress is central to BA’s molecular and cellular anticancer activities
ER Stress↑,
TumCG↓, Cell cycle arrest, growth inhibition, apoptosis induction, and control of inflammation are all the effects of BA’s altered gene expression
Apoptosis↑,
Inflam↓,
ChemoSen↑, BA has additional synergistic effects, increasing both the sensitivity and cytotoxicity of doxorubicin and cisplatin
Casp↑, BA decreases viability and induces apoptosis by activat- ing the caspase-dependent pathway in human pancreatic cancer (PC) cell lines
ERK↓, BA might inhibit the activation of Ak strain transforming (Akt) and extracellular signal–regulated kinase (ERK)1/2,
cl‑PARP↑, initiation of cleavage of PARP were prompted by the treatment with AKBA
AR↓, AKBA affects the androgen receptor by reducing its expression,
cycD1/CCND1↓, decrease in cyclin D1, which inhibits cellular proliferation
VEGFR2↓, In prostate cancer, the downregulation of vascular endothelial growth factor receptor 2–mediated angiogenesis caused by BA
CXCR4↓, Figure 6
radioP↑,
NF-kB↓,
VEGF↓,
P21↑,
Wnt↓,
β-catenin/ZEB1↓,
Cyt‑c↑,
MMP2↓,
MMP1↓,
MMP9↓,
PI3K↓,
MAPK↓,
JNK↑,
*5LO↓, Table 1 (non cancer)
*NRF2↑,
*HO-1↑,
*MDA↓,
*SOD↑,
*hepatoP↑, Preclinical studies demonstrated hepatoprotective impact for BA against different models of hepatotoxicity via tackling oxidative stress, and inflammatory and apoptotic indices
*ALAT↓,
*AST↓,
*LDH↑,
*CRP↓,
*COX2↓,
*GSH↑,
*ROS↓,
*Imm↑, oral administration of biopolymeric fraction (BOS 200) from B. serrata in mice led to immunostimulatory effects
*Dose↝, BA at low concentration tend to stimulate an immune response, as those utilized in the study of Beghelli et al. (2017) however, utilizing higher concentration suppressed the immune response
*eff↑, Useful actions on skin and psoriasis
*neuroP↑, AKBA has substantially diminished the levels of inflammatory markers such as 5-LOX, TNF-, IL-6, and meliorated cognition in lipopolysaccharide-induced neuroinflammation rodent models
*cognitive↑,
*IL6↓,
*TNF-α↓,

2768- Bos,    Boswellic acids as promising agents for the management of brain diseases
- Review, Var, NA - Review, AD, NA - Review, Park, NA
*neuroP↑, BAs-induced neuroprotection is proposed to be associated with the ability to reduce neurotoxic aggregates, decrease oxidative stress, and improve cognitive dysfunction.
*ROS↓,
*cognitive↓,
TumCP↓, BAs have been suggested as potential agents for the treatment of brain tumors due to their potential to attenuate cell proliferation, migration, metastasis, angiogenesis, and promote apoptosis during both in vitro and in vivo studies
TumCMig↓,
TumMeta↓,
angioG↓,
Apoptosis↑,
*Inflam↓, The anti-inflammatory activities of BAs have been investigated in many preclinical and clinical trials
IL1↓, BAs inhibit the production of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-2, IL-4, IL-6, and tumor necrosis factor-α (TNF-α) in several experimental studies.
IL2↓,
IL4↓,
IL6↓,
TNF-α↓,
P53↑, AKBA has been reported to induce apoptosis in pancreatic and gastric cancers, through tumor suppressor protein 53 (p53)-independent pathway, while reducing expression of protein kinase (PK) B and NF-kb
Akt↓,
NF-kB↓,
DNAdam↑, DNA fragmentation, and activation of caspase cascade
Casp↑,
COX2↓, regulated genes such as cyclooxygenase-2 (COX-2), matrix metallopeptidase-9 (MMP-9), C-X-C motif chemokine receptor 4 (CXCR4), and vascular endothelial growth factor (VEGF)
MMP9↓,
CXCR4↓,
VEGF↓,
*SOD↑, BAs against oxidative injury has been shown in several cell lines and animal models [12], [13], [21]. BAs exert protective effects through the normalization of antioxidant enzyme levels, such as superoxide dismutase (SOD), catalase, and glutathione p
*Catalase↑,
*GPx↑,
*NRF2↑, Moreover, it can activate nuclear factor erythroid 2-related factor-2 (Nrf2)/antioxidant response element-regulated pathways

1448- Bos,    A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells
- in-vitro, AML, HL-60
TumCP↓,
Apoptosis↑,
ROS↑, initial events involved massive reactive oxygen species (ROS) and nitric oxide (NO) formation
NO↑,
cl‑Bcl-2↑,
BAX↑, translocation of Bax to mitochondria
MMP↓, loss of mitochondrial membrane potential
Cyt‑c↑, release of cytochrome c to the cytosol
AIF↑, release to the cytosol
Diablo↑, release to the cytosol
survivin↓,
ICAD↓,
Casp↑,
cl‑PARP↑,
DR4↑,
TNFR 1↑,

1450- Bos,  Cisplatin,    3-Acetyl-11-keto-β-boswellic acid (AKBA) induced antiproliferative effect by suppressing Notch signaling pathway and synergistic interaction with cisplatin against prostate cancer cells
- in-vitro, Pca, DU145
ROS↑, increased reactive oxygen species (ROS) generation
MMP↓,
Casp↑,
Apoptosis↑,
Bax:Bcl2↑,
TumCCA?, induce G0/G1 arrest
cycD1/CCND1↓,
CDK4↓,
P21↑,
p27↑,
NOTCH↓, AKBA demonstrated significant downregulation of Notch signaling mediators
ChemoSen↑, AKBA has the potential to synergistically enhance the cytotoxic efficacy of cisplatin

5739- Buty,    Butyrate as a promising therapeutic target in cancer: From pathogenesis to clinic (Review)
- Review, Var, NA
GutMicro↑, Butyrate, a short-chain fatty acid, is generated through gut microbial fermentation of dietary fiber.
*Inflam↓, Butyrate, a primary anti-inflammatory SCFA, exhibits a multifaceted role in mitigating inflammation
*IL6↓, It inhibits the production of pro-inflammatory cytokines and chemokines, such as IL-6, TNF-α and IL-17, which helps to prevent colon cancer
*TNF-α↓,
*IL17↓,
*IL10↑, while promoting IL-10 production
*ROS↝, regulates the production of reactive oxygen species (ROS)
COX2↓, butyrate has been observed to suppress inflammation by inhibiting the expression of cyclooxygenase-2 mRNA in colonic tissues (60).
NLRP3↓, butyrate exhibits the highest efficiency in the negative regulation of NLRP3
Imm↑, Enhancement of the immunotherapeutic effect
HDAC↓, Inhibition of HDAC activity in cells
TumCCA↑, Butyrate has been found to induce cell cycle arrest in the G0/G1 phase in a dose-dependent manner in vitro in numerous tumors, including colon, liver, lung and bladder cancer,
Apoptosis↑, butyrate-induced apoptosis is accompanied by elevated ROS levels and caspase activity (126)
ROS↑,
Casp↑,
mtDam↑, suggests that ROS can induce mitochondrial membrane damage, release Cyt c from damaged mitochondria, and enhance apoptosis via the Cyt c/caspase-3 pathway
Cyt‑c↑,
eff↑, Clostridium butyricum is an anaerobic bacterium classified as a probiotic due to its production of butyric acid (139)
chemoP↑, butyrate not only alleviates the side effects associated with conventional chemotherapeutic agents such as oxaliplatin, irinotecan and 5-fluorouracil (149-151), but it also enhances the efficacy of both chemotherapy and immunotherapy
ChemoSen↑,
eff↑, metformin has been demonstrated to enhance the biosynthesis of butyrate while concurrently inhibiting the progression of CRC
RadioS↑, Butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone.
HCAR2↑, Activation of cell-surface receptors (GPR41, GPR43 and GPR109A);

1651- CA,  PBG,    Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer
- Review, Var, NA
Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate combination at high temperatures. However, a low amount of CA is yielded via this pathway
eff↝, Decyl CA (DCA) is a novel derivative of CA but its role in affecting colorectal cancer has not been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM) can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 μM) and metformin (10 mM) is of interest in cervical squamous cell carcinoma therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.

5923- CA,  RosA,    Rosemary as a Potential Source of Natural Antioxidants and Anticancer Agents: A Molecular Docking Study
- Review, Var, NA
TumCD↑, CA, it has the capacity to induce cell death of cancer cells through the rise in ROS levels within the cells, the inhibition of protein kinase AKT, the activation of autophagy-related genes (ATG) and the disrupt mitochondrial membrane potential.
ROS↑,
Akt↓,
ATG3↑,
MMP↓,
Casp↑, RA, its antitumor actions encompass apoptosis induction through caspase activation, the inhibition of cell proliferation by interrupting cell cycle progression and epigenetic regulation, antioxidative stress-induced DNA damage, and interference with
TumCP↓,
TumCCA↑,
DNAdam↑,
angioG↓,

5835- CAP,    Capsaicin and dihydrocapsaicin induce apoptosis in human glioma cells via ROS and Ca2+-mediated mitochondrial pathway
- in-vitro, GBM, U251
tumCV↓, Treatment of U251 glioma cells with Cap and DHC resulted in a dose- and time-dependent inhibition of cell viability and induction of apoptosis,
Apoptosis↑,
selectivity↑, whereas few effects were observed on the viability of L929 normal murine fibroblast cells.
ROS↑, The apoptosis-inducing effects of Cap and DHC in U251 cells were associated with the generation of reactive oxygen species, increased Ca2+ concentrations, mitochondrial depolarization, release of cytochrome c into the cytosol and activation of caspas
Ca+2↑, Cap and DHC treatment increases ROS generation and [Ca2+]i in U251 cells
MMP↓,
Cyt‑c↑,
Casp↑,
eff↑, DHC, an analog of Cap, inhibits the proliferation of HCT116, MCF-7 and WI38 cells more potently than Cap,
MPT↑, High levels of Ca2+ can open mitochondrial permeability transition pores, depolarize mitochondrial membrane potential, activate caspase-9 and caspase-3, initiate the mitochondrial apoptosis pathway, to induce cell apoptosis
ETC↓, Cap boosts the generation of ROS in human pancreatic cancer cells by inhibiting mitochondrial complex I and III and destroying mitochondrial functions
Casp3↑, elease of cyto c to the cytosol to activate caspase-9 and −3
Casp9↑,

5831- CAP,    Unraveling TRPV1’s Role in Cancer: Expression, Modulation, and Therapeutic Opportunities with Capsaicin
TRPV1↑, Activation of TRPV1 triggers calcium influx and affects cell signaling linked to growth and death.
Ca+2↑,
AntiCan↑, Capsaicin has been extensively studied for its anti-cancer effects, such as inhibiting cell proliferation and modulating cancer-related pain.
TumCP↓,
Pain↓,
TumCG↓, reduced tumor growth and enhanced chemosensitivity, positioning it as a promising adjunct in cancer therapy
ChemoSen↑, Capsaicin sensitizes cancer cells to chemotherapy drugs, thereby improving therapeutic outcomes [25]
Apoptosis↑, apsaicin-induced TRPV1 activation triggers apoptosis in colorectal cancer cells through the calcineurin–NFAT2–p53 signaling pathway [39]
ROS↑, Increased intracellular calcium from TRPV1 activation causes mitochondrial overload, leading to disrupted function, elevated ROS, loss of membrane potential, and cytochrome C release [Figure 2].
MMP↓,
Cyt‑c↑,
Casp↑, This triggers caspase activation and cell death.

5826- CAP,    Capsaicin induces mitochondrial dysfunction and apoptosis in anaplastic thyroid carcinoma cells via TRPV1-mediated mitochondrial calcium overload
- in-vitro, Thyroid, NA
TRPV1↑, we reported that capsaicin (CAP), a transient receptor potential vanilloid type1 (TRPV1) agonist, inhibited the viability of anaplastic thyroid cancer cells.
tumCV↓,
Ca+2↑, Capsaicin treatment triggered Ca2+ influx by TRPV1 activation, resulting in disequilibrium of intracellular calcium homeostasis.
mtDam↑, In addition, the disruption of mitochondrial calcium homeostasis caused by capsaicin led to mitochondrial dysfunction in ATC cells
ROS↑, as evidenced by the production of mitochondrial reactive oxygen species (ROS), depolarization of mitochondrial membrane potential (ΔΨm), and opening of mitochondrial permeability transition pore (mPTP)
MMP↓,
MPT↑,
Cyt‑c↑, the resulting release of cyt c into the cytosol triggered apoptosome assembly and subsequent caspase activation and apoptosis.
Casp↑,
Apoptosis↑,

5858- CAP,    Capsaicin as a Microbiome Modulator: Metabolic Interactions and Implications for Host Health
- Review, Nor, NA - Review, AD, NA
*BBB↓, crosses the blood–brain barrier, alters neurotransmitter levels, and accumulates in brain regions involved in cognition.
*GutMicro↑, capsaicin appears to undergo microbial transformation and influences gut microbial composition, favoring short-chain fatty acid producers and suppressing pro-inflammatory taxa. often favoring the growth of beneficial taxa such as Ruminococcaceae, Lac
Obesity↓, These changes contribute to anti-obesity, anti-inflammatory, and potentially anticancer effects
*Inflam↓,
*AntiCan↑,
*TRPV1↑, Capsaicin is a potent agonist perceived by TRPV1, a transmembrane cation channel that functions with Ca2+.
*Ca+2↑, causes an increase in Ca2+ flux,
*antiOx↑, Capsaicin is a bioactive compound of chili peppers responsible for their spicy flavor, which also shows antioxidant, anti-obesity, analgesic, anti-inflammatory, anticarcinogenic, and cardioprotective effects
*cardioP↑,
*BioAv↓, capsaicin exhibits low systemic bioavailability due to its rapid metabolism in the liver and other tissues, resulting in a short plasma half-life of approximately 25 min in humans
*Half-Life↓,
*BioAv↝, Capsaicin’s bioavailability is determined by multiple interrelated factors, including its physicochemical properties, metabolic transformations, route of administration, and the biological context of the host, including gut microbiota composition.
*BioAv↑, For instance, polymeric micelles, liposomes, and hydroxypropyl-β-cyclodextrin complexes have demonstrated the capacity to enhance capsaicin’s oral bioavailability, prolong its plasma half-life, and improve therapeutic consistency
*neuroP↑, capsaicin exposure alters glutamate, GABA, and serotonin levels in distinct brain regions, with potential implications for neuroprotection, mood regulation, and energy metabolism.
Apoptosis↑, apoptosis is the main mechanism by which capsaicin induces cell death in cancer cells.
p38↑, capsaicin triggers a calcium flux within the cell via TRPV1, activating the p38 pathway.
ROS↑, As a result, reactive oxygen species (ROS) are produced, along with depolarization of the mitochondrial membrane potential and opening of the mitochondrial permeability transition pore.
MMP↓,
MPT↑,
Cyt‑c↑, Consequently, cytochrome c is released, the apoptosome is assembled, and caspases are activated, ultimately leading to cell death
Casp↑,
TRIB3↑, capsaicin enhances TRIB3 gene expression, which allowed an increase in the antiproliferative and proapoptotic effects of TRIB3 in cancer cells
NADH↓, Capsaicin has also been seen to downregulate and inhibit tumor-associated NADH oxidase (tNOX) and Sirtuin1 (SIRT1) in multiple cancer cell lines such as bladder cancer, which led to reduced cell growth and migration
SIRT1↓,
TumCG↓,
TumCMig↓,
TOP1↓, pointing out that capsaicin had an inhibitory effect on topoisomerases I and II, causing a reduction in metabolic activity and proliferation of a human colon cancer cell line
TOP2↓,
β-catenin/ZEB1↓, with capsaicin, the β-catenin transcription gets downregulated
*ROS↓, Capsaicin has also been proven to alleviate redox imbalance or oxidative stress, thanks to its antioxidative activity.
*Aβ↓, Alsheimer’s disease, attenuating neurodegeneration in mice by reducing amyloid-beta levels via the promotion of non-amyloidogenic processing of amyloid precursor protein

5845- CAP,    Unveiling the Molecular Mechanisms Driving the Capsaicin-Induced Immunomodulatory Effects on PD-L1 Expression in Bladder and Renal Cancer Cell Lines
- in-vivo, RCC, A498 - in-vitro, RCC, T24/HTB-9 - NA, Bladder, 5637
TRPV1↑, CPS has been found to induce both carcinogenic and anti-carcinogenic effects in a transient receptor potential vanilloid subtype 1 (TRPV1)-dependent and -independent manner [7,8,9,10,11].
TumCP↓, CPS at high doses reduces proliferation of RCCs in a TRPV1-dependent manner, induces caspase-dependent apoptosis and growth of 786-O RC xenografts in vivo
Casp↑,
Apoptosis↑,
SIRT1↓, Moreover, by downregulating SIRT1, CPS enhances the acetylation of cortactin and β-catenin to decrease MMP-2 and MMP-9 activation and impair cell migration in BC cells [15,16].
MMP2↓,
MMP9↓,
TumCMig↓,
TumCCA↑, CPS suppresses cell proliferation, and induces cell cycle arrest and reactive oxygen species (ROS) production in BC cells, through FOXO3a-mediated pathways [17,18].
ROS↑,
DNAdam↑, CPS Induces DNA Damage in Living 5637, T24 and A498 Cancer Cell Lines
PD-L1↑, We found that CPS increased the PD-L1 expression, both at mRNA and protein levels, in T24 and 5637 cells
eff↓, ROS generation was completely reverted by NAC in CPS-treated A498 cells at 3–6 h treatment

5199- CAP,    Capsaicin is a novel blocker of constitutive and interleukin-6-inducible STAT3 activation
- vitro+vivo, AML, NA
STAT3↓, We found that capsaicin inhibited constitutive activation of STAT3 in multiple myeloma cells in a dose- and time-dependent manner
cycD1/CCND1↓, Capsaicin down-regulated the expression of the STAT3-regulated gene products, such as cyclin D1, Bcl-2, Bcl-xL, survivin, and vascular endothelial growth factor.
Bcl-2↓,
Bcl-xL↓,
survivin↓,
VEGF↓,
TumCCA↑, capsaicin induced the accumulation of cells in G(1) phase, inhibited proliferation, and induced apoptosis, as indicated by caspase activation.
Apoptosis↑,
Casp↑,
eff↑, Capsaicin also significantly potentiated the apoptotic effects of Velcade and thalidomide in multiple myeloma cells.

5887- CAR,  TV,    Antitumor Effects of Carvacrol and Thymol: A Systematic Review
- Review, Var, NA
Apoptosis↑, It was attested that carvacrol and thymol induced apoptosis, cytotoxicity, cell cycle arrest, antimetastatic activity,
TumCCA↑, accumulation of cells in the G1 phase, together with a reduction of cells in the S phase, slowing cell cycle/mitosis and provoking cell death.
TumMeta↓,
TumCP↓, antiproliferative effects and inhibition of signaling pathways (MAPKs and PI3K/AKT/mTOR).
MAPK↓,
PI3K↓,
Akt↓,
mTOR↓,
eff↑, carvacrol appears to be more potent than thymol
*Inflam↓, these compounds present anti-inflammatory (Li et al., 2018; Chamanara et al., 2019) and antioxidant
*antiOx↑,
AXL↓, These effects occurred mainly through the inhibition of tyrosine kinase receptor (AXL) expression and an increase in malondialdehyde (MDA
MDA↑,
Casp3↑, caspase-3 activation and Bcl-2 inhibition
Bcl-2↓,
MMP2↓, promoted a decrease in Bcl-2, metalloproteinase-2 and -9 (MMP-2 and MMP-9), p-ERK, p-Akt, cyclin B1 levels and an increase in p-JNK, Bax levels, resulting in cell cycle arrest at the G2/M phase
MMP9↓,
p‑JNK↑,
BAX↑,
MDA↓, In respect of breast cancer, treatment with carvacrol decreases MDA-MB231 (Jamali et al., 2018; Li et al., 2021) and MCF-7 cells line viability
TRPM7↓, TRPM7 pathway is one of the suggested pharmacological mechanisms of action
MMP↓, decreased mitochondrial membrane potential, cytochrome C release, caspase activation, PARP cleavage
Cyt‑c↑,
Casp↑,
cl‑PARP↑,
ROS↑, Carvacrol also induced cytotoxicity and apoptosis (via caspase-3 and reactive oxygen species—ROS) of human oral squamous cell carcinoma (OC2 cell line)
CDK4↓, In tongue cancer (Tca-8113, SCC-25 cell lines), Dai et al. (2016) reported that carvacrol effectively inhibited cell proliferation through the negative regulation of CCND1 and CDK4 expression, and the positive regulation of p21 expression,
P21↑,
F-actin↓, A blockade of TRPM7 channels, reduced expression of MMP-2 and F-actin, was also observed, together with the inhibition of PI3K/Akt and MAPK
GSH↓, by increasing ROS, Bax, Caspase-3, -9 levels and reducing Bcl-2 and GSH levels.
*SOD↑, Moreover, carvacrol was able to increase the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH), along with a reduction of lipid peroxides and the enzymes AST, ALT, AL
*Catalase↑,
*GPx↑,
*GSR↑,
*GSH↑,
*lipid-P↓,
*AST↓,
*ALAT↓,
*ALP↓,
*LDH↓,
DNAdam↑, hepatocellular carcinoma induced by diethylnitrosamine (DEN), carvacrol treatment promoted DNA fragmentation
AFP↓, carvacrol showed a reduction in serum levels of alpha-fetoprotein (AFP), alpha l-fucosidase (AFU), vascular endothelial growth factor (VEGF
VEGF↓,
Weight↑, Carvacrol supplementation significantly improved the weight gain and growth rate of animals with colon cancer
*chemoP↑, reduction in oxidative stress damage (higher levels of GSH, GPx, GR, SOD and CAT), suggesting that carvacrol presents chemopreventive effects
ROS↑, In vitro, carvacrol and thymol increased the generation of reactive oxygen species in 24.63% (n = 17) of the studies, a fact that is also observed in chemotherapeutics

5880- CAR,    In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis
- vitro+vivo, Lung, A549 - in-vitro, Nor, BEAS-2B - in-vitro, Lung, PC9
Dose↝, prepare a carvacrol nanoemulsion (CANE) using an ultrasonication technique and further evaluation of its anticancer potential against human lung adenocarcinoma A549 cells. (160nm)
mt-ROS↑, The CANE induced reactive oxygen species (ROS) production in A549 cells,
p‑JNK↑, leading to activation of key regulators of apoptosis such as p-JNK, Bax and Bcl2 as well as release of cytochrome C, and activation of the caspase cascade.
BAX↑,
Cyt‑c↑,
Casp↑,
AntiTum↑, CANE displayed a strong antitumor potential in vivo using an athymic nude mice model.
ER Stress↑, Abnormally high ROS levels create ER stress with the involvement of three major signaling proteins IRE1-α, PERK and ATF-6
LDH↑, higher LDH activity, which is a well-established biomarker released by damaged cells, was observed in CANE-treated cells
selectivity↑, CANE displayed no cytotoxicity up to 100 µg/ml against normal bronchial epithelium cells (BEAS-2B)
Apoptosis↑, Induction of apoptosis and ROS production in the presence of CANE
DNAdam↑, potential role on DNA damage and chromatin condensation
IRE1↑, We observed a higher expression of IRE1-α in CANE treated cells
XBP-1↑, similar expression pattern for XBP-1
CHOP↓, down-regulation of CHOP, p-eIF2α, and GRP78 was observed in CANE-treated cells
p‑eIF2α↓,
GRP78/BiP↓,
Ca+2↑, increase of Ca+2 levels in CANE-treated cells. A 2.5 fold higher Ca+2 was observed at 100 μg/ml CANE treated cells
MMP↓, CANE severely altered mitochondrial membrane potential (Δψm) in a dose-dependent manner.
Bcl-2↓, up- and down-regulation of pro-apoptotic (Bax) and anti-apoptotic (Bcl2) proteins
Casp3↑, higher levels of cleaved caspase-9 and caspase-3 in cells treated with CANE in a dose-dependent manner
Casp9↑,
eff↓, To confirm this, A549 cells were first treated with N-acetyl-L-cysteine NAC (5 mM), a strong scavenger of ROS, prior to CANE (100 µg/ml) treatment and observed a marked reduction in ROS generation
TumW↓, A significant (p < 0.05) 34.2 and 62.1% reduction in tumor weight was observed in the mice treated with 50 and 100 mg/Kg CANE, orally three times in a week
Weight↑, body weights of 100 mg/kg CANE treated mice remained static up to the second week and increased further up to 4 weeks
eff↑, ultrasonication consider as simple, cost-effective, clean and prompt aseptic technique16, wherein large droplets ruptured into small droplets by ultrasound leading to the formation of nano-scale droplets
eff↑, We selected polysorbate 80 as a surfactant (HLB, 15), which is regarded as safe for using in pharmaceutical and food industries1

5907- CAR,    Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2
- in-vitro, Liver, HepG2
TumCG↓, In this study, we showed that carvacrol inhibited HepG2 cell growth by inducing apoptosis
Apoptosis↓,
Casp3↓, activation of caspase-3, cleavage of PARP and decreased Bcl-2 gene expression
cl‑PARP↑,
Bcl-2↓,
p‑ERK↓, decreasing phosphorylation of ERK1/2 significantly in a dose-dependent manner, and activated phosphorylation of p38
p‑p38↑,
*Bacteria↓, carvacrol has been shown to exhibit anti-microbial, anti-mutagenic, anti-platelet, analgesic, anti-inflammatory, anti-angiogenic, anti-oxidant, anti-elastase, insecticidal, anti-parasitic,cell-protective, AChE inhibitor and anti-tumor activity
*AntiAg↑,
*Inflam↓,
*antiOx↑,
*AChE↓,
AntiTum↑,
MMP↓, classical apoptosis response, including decrease in mitochondrial membrane potential and increase in cytochrome c release from mitochondria, decrease in Bcl-2/Bax ratio, increase in caspase activity and cleavage of PARP and fragmentation of DNA,
Cyt‑c↑,
Bax:Bcl2↑,
Casp↑,
DNAdam↑,
selectivity↑, we found that carvacrol induced stronger effects on hepatocellular carcinoma cells compared to normal human fetal liver cells.

5903- CAR,  TV,    Combined Cytotoxic Effects of Carvacrol-Based Essential Oil Formulations
- in-vitro, BC, MDA-MB-231
BioAv↑, Combined effects of carvacrol with α-pinene, eugenol, and β-terpineol likely contributed to enhanced bioactivity.
MPT↑, Compounds such as thymol, α-pinene, eugenol, β-terpineol, and camphene have been shown to enhance membrane permeability, modulate redox signaling, potentiate ROS-mediated cell death, and amplify caspase activation
ROS↑,
Casp↑,
eff↑, including cinnamon oil (cinnamaldehyde) and peppermint oil (menthol/menthone), which may contribute to combined effects with carvacrol to modulate cellular processes
PI3K↓, In MCF-7 cells, carvacrol has been reported to inhibit the PI3K/AKT pathway, halting the cell cycle and inducing apoptosis.
Akt↓,
TumCCA↑,
Apoptosis↑,
Cyt‑c↑, decrease in membrane potential, cytochrome-c release, caspase activation, and PARP cleavage in a concentration-dependent manner
cl‑PARP↑,
MPT↑, Thymol and α-pinene can increase cell membrane permeability, thereby enhancing cytotoxic effects

5921- Cats,    Effect of Uncaria tomentosa Extract on Apoptosis Triggered by Oxaliplatin Exposure on HT29 Cells
- in-vitro, Colon, HT29
ChemoSen↑, The hydroalcoholic extract of Uncaria tomentosa enhanced chemotherapy-induced apoptosis,
Casp↑, n increase in caspase activities, and an increase of DNA fragments in culture of the neoplastic cells.
DNAdam↑,
ROS↑, The ROS content was significantly increased in comparison with the control with treatment of the Uncaria tomentosa extract plus oxaliplatin

4493- Chit,  Selenate,  Se,    A novel synthetic chitosan selenate (CS) induces apoptosis in A549 lung cancer cells via the Fas/FasL pathway
- in-vitro, Lung, A549
tumCV↓, CS could significantly inhibit A549 cells viability in a dose-dependent manner.
Apoptosis↑, CS induced cell death via apoptosis and not necrosis.
TumCCA↑, CS triggered S and G2/M phase arrest in a dose-dependent manner
Fas↑, CS up-regulated the expression levels of Fas, FasL, and Fadd
FasL↑,
FADD↑,
Casp↑, activated the caspase cascade in A549 cells

6068- CHL,    Dietary chlorophyllin inhibits the canonical NF-κB signaling pathway and induces intrinsic apoptosis in a hamster model of oral oncogenesis
- in-vivo, Oral, NA
NF-kB↓, Dietary administration of chlorophyllin (4 mg/kg bw) suppressed the development of HBP carcinomas by inhibiting the canonical NF-κB signaling pathway by downregulating IKKβ, preventing the phosphorylation of IκB-α, and reducing NF-κB
IKKα↓,
Apoptosis↓, Inactivation of NF-κB signaling by chlorophyllin was associated with the induction of intrinsic apoptosis as evidenced by modulation of Bcl-2 family proteins
Bcl-2↑,
survivin↓, enforced nuclear localization of survivin, upregulation of apoptogenic molecules, activation of caspases, and cleavage of PARP.
Casp↑,
cl‑PARP↑,


Showing Research Papers: 1 to 50 of 114
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 114

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

ATF3↓, 1,   Ferroptosis↑, 1,   GPx4↓, 1,   GSH↓, 4,   HO-1↓, 1,   c-Iron↑, 1,   lipid-P↓, 1,   lipid-P↑, 2,   MDA↓, 1,   MDA↑, 1,   NADH↓, 1,   NQO1↓, 1,   NRF2↓, 2,   ROS↑, 35,   ROS⇅, 1,   mt-ROS↑, 1,   SOD↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 5,   ATP↓, 3,   ETC↓, 1,   MEK↓, 1,   MMP↓, 26,   MPT↑, 6,   mtDam↑, 3,   Raf↓, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4↑, 1,   AMPK↑, 1,   p‑AMPK↑, 1,   cMyc↓, 1,   FASN↓, 2,   Glycolysis↓, 1,   H2S↑, 1,   HK2↓, 1,   HMG-CoA↓, 1,   lactateProd↓, 1,   LDH↑, 1,   LDL↓, 1,   NADPH↓, 1,   PPARγ↑, 1,   SIRT1↓, 2,  

Cell Death ⓘ

Akt↓, 11,   p‑Akt↓, 1,   APAF1↑, 1,   Apoptosis↓, 2,   Apoptosis↑, 33,   mt-Apoptosis↑, 2,   Bak↑, 1,   BAX↑, 13,   Bax:Bcl2↑, 4,   Bcl-2↓, 16,   Bcl-2↑, 1,   cl‑Bcl-2↑, 1,   Bcl-xL↓, 3,   BIM↑, 1,   Casp↑, 49,   cl‑Casp↑, 1,   Casp3↓, 1,   Casp3↑, 7,   cl‑Casp3↑, 1,   cl‑Casp7↑, 1,   Casp8↑, 1,   cl‑Casp8↑, 1,   Casp9↑, 3,   cl‑Casp9↑, 1,   CK2↓, 2,   Cyt‑c↑, 25,   Diablo↑, 2,   DR4↑, 1,   DR5↑, 1,   FADD↑, 1,   Fas↑, 3,   FasL↑, 1,   Ferroptosis↑, 1,   hTERT/TERT↓, 1,   IAP1↓, 1,   cl‑IAP2↑, 1,   ICAD↓, 1,   iNOS↓, 1,   JNK↓, 1,   JNK↑, 4,   p‑JNK↓, 1,   p‑JNK↑, 2,   MAPK↓, 4,   MAPK↑, 4,   MDM2↓, 1,   p27↑, 2,   p38↓, 1,   p38↑, 4,   p‑p38↑, 1,   survivin↓, 8,   Telomerase↓, 1,   TNFR 1↑, 1,   TRPV1↑, 3,   TumCD↑, 1,  

Kinase & Signal Transduction ⓘ

HCAR2↑, 1,   HER2/EBBR2↓, 1,   Sp1/3/4↓, 3,  

Transcription & Epigenetics ⓘ

ac‑H3↑, 1,   ac‑H4↑, 1,   PhotoS↑, 1,   p‑pRB↓, 1,   tumCV↓, 6,  

Protein Folding & ER Stress ⓘ

CHOP↓, 1,   CHOP↑, 1,   p‑eIF2α↓, 1,   ER Stress↑, 5,   GRP78/BiP↓, 1,   HSPs↓, 1,   IRE1↑, 1,   XBP-1↑, 1,  

Autophagy & Lysosomes ⓘ

ATG3↑, 1,   LC3B-II↑, 1,   LC3II↑, 1,   p62↓, 1,   TumAuto↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 14,   P53↓, 2,   P53↑, 9,   p‑P53↑, 2,   PARP↑, 2,   cl‑PARP↑, 10,   γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK4↓, 5,   CDK4↑, 1,   Cyc↓, 1,   CycB/CCNB1↑, 1,   cycD1/CCND1↓, 6,   cycE/CCNE↓, 1,   P21↑, 10,   RB1↑, 1,   TFAP2A↓, 1,   TumCCA?, 1,   TumCCA↓, 1,   TumCCA↑, 19,  

Proliferation, Differentiation & Cell State ⓘ

ALDH1A1↓, 1,   BMI1↓, 1,   CD133↓, 1,   CD44↓, 1,   CSCs↓, 3,   EMT↓, 4,   ERK↓, 3,   ERK↑, 1,   p‑ERK↓, 3,   FOXO↑, 1,   GSK‐3β↓, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 3,   HMGCR↓, 1,   IGF-1↓, 1,   IGFBP3↑, 1,   mTOR↓, 4,   Nanog↓, 1,   NOTCH↓, 1,   NOTCH1↓, 2,   OCT4↓, 1,   PI3K↓, 7,   PTEN↑, 1,   RAS↓, 1,   SOX2↓, 1,   STAT3↓, 3,   TOP1↓, 3,   TOP2↓, 1,   TRPM7↓, 1,   TumCG↓, 10,   Wnt↓, 3,  

Migration ⓘ

AntiAg↑, 1,   AXL↓, 1,   Ca+2↑, 10,   cal2↑, 1,   E-cadherin↑, 2,   ER-α36↓, 1,   F-actin↓, 1,   FAK↓, 1,   ITGB4↓, 1,   LAMs↓, 1,   MMP1↓, 1,   MMP2↓, 8,   MMP9↓, 9,   MMPs↓, 1,   ROCK1↓, 1,   TGF-β↓, 1,   TRIB3↑, 1,   TSP-1↑, 1,   TumCI↓, 3,   TumCMig↓, 8,   TumCP↓, 11,   TumMeta↓, 5,   Twist↓, 1,   Vim↓, 2,   β-catenin/ZEB1↓, 7,  

Angiogenesis & Vasculature ⓘ

angioG↓, 6,   angioG↑, 1,   ATF4↑, 1,   EGFR↓, 2,   EPR↑, 3,   HIF-1↓, 1,   Hif1a↓, 3,   Hif1a↑, 1,   NO↓, 1,   NO↑, 1,   VEGF↓, 13,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 6,   CRP↓, 1,   CXCR4↓, 3,   HCAR2↑, 1,   IFN-γ↓, 1,   IKKα↓, 1,   IL1↓, 1,   IL12↑, 1,   IL1β↓, 1,   IL2↓, 1,   IL2↑, 1,   IL4↓, 1,   IL6↓, 3,   Imm↑, 2,   Inflam↓, 1,   JAK2↓, 1,   NF-kB↓, 12,   NF-kB↑, 1,   p65↓, 1,   PD-L1↓, 1,   PD-L1↑, 1,   PSA↓, 1,   TNF-α↓, 4,   TNF-α↑, 1,  

Protein Aggregation ⓘ

NLRP3↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   CDK6↓, 1,   CDK6↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 3,   BioAv↑, 6,   BioEnh↑, 1,   ChemoSen↓, 1,   ChemoSen↑, 19,   Dose↝, 3,   Dose∅, 1,   eff↓, 5,   eff↑, 25,   eff↝, 1,   MDR1↓, 1,   MRP1↓, 1,   RadioS↑, 5,   selectivity↑, 9,  

Clinical Biomarkers ⓘ

AFP↓, 1,   AR↓, 2,   CRP↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 2,   GutMicro↑, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 1,   IL6↓, 3,   LDH↑, 1,   PD-L1↓, 1,   PD-L1↑, 1,   PSA↓, 1,   TRIB3↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 4,   AntiTum↑, 4,   chemoP↑, 4,   chemoPv↑, 1,   hepatoP↑, 1,   NDRG1↑, 1,   Obesity↓, 1,   OS↑, 1,   Pain↓, 1,   QoL↑, 1,   radioP↑, 1,   Remission↑, 1,   Risk↓, 1,   toxicity↓, 1,   toxicity↝, 1,   TumVol↓, 2,   TumW↓, 3,   Weight↑, 2,  
Total Targets: 281

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 4,   Catalase↑, 2,   GPx↑, 2,   GSH↑, 2,   GSR↑, 1,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 3,   ROS↓, 4,   ROS↝, 1,   ROS∅, 1,   SOD↑, 3,   SOD2↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 2,   LDH↓, 1,   LDH↑, 1,  

Cell Death ⓘ

MAPK↓, 1,   TRPV1↑, 1,  

Migration ⓘ

5LO↓, 1,   AntiAg↑, 2,   Ca+2↑, 1,   PKCδ↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL10↑, 1,   IL17↓, 1,   IL6↓, 2,   Imm↑, 1,   Inflam↓, 6,   TNF-α↓, 2,  

Synaptic & Neurotransmission ⓘ

AChE↓, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   BioAv↝, 1,   Dose↝, 1,   eff↑, 1,   Half-Life↓, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 2,   ALP↓, 1,   AST↓, 2,   CRP↓, 1,   GutMicro↑, 2,   IL6↓, 2,   LDH↓, 1,   LDH↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 2,   chemoP↑, 2,   cognitive↓, 1,   cognitive↑, 1,   hepatoP↑, 1,   neuroP↑, 3,  

Infection & Microbiome ⓘ

Bacteria↓, 1,  
Total Targets: 56

Scientific Paper Hit Count for: Casp, caspase
7 Thymoquinone
6 Betulinic acid
6 Capsaicin
5 Fisetin
4 Silver-NanoParticles
4 Boswellia (frankincense)
4 Carvacrol
4 Shikonin
3 Allicin (mainly Garlic)
3 Alpha-Lipoic-Acid
3 Apigenin (mainly Parsley)
3 Propolis -bee glue
3 Gambogic Acid
3 Selenite (Sodium)
3 Sulforaphane (mainly Broccoli)
2 Berberine
2 Cisplatin
2 Rosmarinic acid
2 Thymol-Thymus vulgaris
2 Selenium
2 Chrysin
2 Curcumin
2 EGCG (Epigallocatechin Gallate)
2 Graviola
2 Nimbolide
2 Parthenolide
2 Quercetin
2 Selenium NanoParticles
2 Silymarin (Milk Thistle) silibinin
2 Urolithin
1 3-bromopyruvate
1 Astragalus
1 alpha Linolenic acid
1 Artemisinin
1 Ashwagandha(Withaferin A)
1 Atorvastatin
1 Bufalin/Huachansu
1 Brucea javanica
1 brusatol
1 borneol
1 Butyrate
1 Caffeic acid
1 Carnosic acid
1 Cat’s Claw
1 chitosan
1 Selenate
1 Chlorophyllin
1 Dichloroacetate
1 Deguelin
1 Ellagic acid
1 Emodin
1 verapamil
1 Genistein (soy isoflavone)
1 Hyperthermia
1 HydroxyTyrosol
1 Luteolin
1 Metformin
1 Magnetic Fields
1 Iron
1 Naringin
1 Phenylbutyrate
1 Phenethyl isothiocyanate
1 Pterostilbene
1 salinomycin
1 irinotecan
1 Photodynamic Therapy
1 doxorubicin
1 Ursolic acid
1 Vitamin C (Ascorbic Acid)
1 Vitamin K2
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:443  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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