PARP Cancer Research Results

PARP, poly ADP-ribose polymerase (PARP) cleavage: Click to Expand ⟱

Source:

Type:

Poly (ADP-ribose) polymerase (PARP) cleavage is a hallmark of caspase activation. PARP (Poly (ADP-ribose) polymerase) is a family of proteins involved in a variety of cellular processes, including DNA repair, genomic stability, and programmed cell death. PARP enzymes play a crucial role in repairing single-strand breaks in DNA.
PARP has gained significant attention, particularly in the treatment of certain types of tumors, such as those with BRCA1 or BRCA2 mutations. These mutations impair the cell's ability to repair double-strand breaks in DNA through homologous recombination. Cancer cells with these mutations can become reliant on PARP for survival, making them particularly sensitive to PARP inhibitors.
PARP inhibitors, such as olaparib, rucaparib, and niraparib, have been developed as targeted therapies for cancers associated with BRCA mutations.

PARP Family:
The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes involved in a number of cellular processes, including DNA repair, genomic stability, and programmed cell death.
PARP1 is the predominant family member responsible for detecting DNA strand breaks and initiating repair processes, especially through base excision repair (BER).

PARP1 Overexpression:
In several cancer types—including breast, ovarian, prostate, and lung cancers—elevated PARP1 expression and/or activity has been reported.
High PARP1 expression in certain cancers has been associated with aggressive tumor behavior and resistance to therapies (especially those that induce DNA damage).
Increased PARP1 activity may correlate with poorer overall survival in tumors that rely on DNA repair for survival.

Scientific Papers found: Click to Expand⟱

5459-

AF,

Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells

in-vitro,

Ovarian,

ROS↑, AF primarily functions as a pro-oxidant by inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in ovarian cancer.
TrxR↓, The primary mechanism of action of auranofin is to act as a pro-oxidative agent, increasing the production of reactive oxygen species (ROS) as a consequence of inhibiting the thioredoxin reductase (TrxR) anti-oxidant system
MMP↓, triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis.
Apoptosis↑,
eff↓, Notably, AF-induced cell death was abrogated by the ROS-scavenger N-acetyl cysteine (NAC).
Casp3↑, lethality of AF was associated with the activation of caspases-3/7 and the generation of DNA damage
Casp7↑,
DNAdam↑,
eff↑, Finally, when AF and L-BSO were combined, we observed synergistic lethality against HGSOC cells, which was mediated by a further increase in ROS and a decrease in the levels of the antioxidant GSH.
GSH↓,
angioG↓, Additionally, auranofin has been shown to inhibit angiogenesis
ChemoSen↑, In this study, we identified the mechanisms of cytotoxicity induced by auranofin in HGSOC cells that have different clinical sensitivities to platinum.
cl‑PARP↑, the cleavage of poly-ADP ribose polymerase (PARP), and the polyubiquitination of proteins
eff↑, synergistic lethal interaction between auranofin and a second pro-oxidant agent, the glutathione (GSH) inhibitor, L-buthionine sulfoximine (L-BSO);

5472-

AF,

Auranofin induces apoptosis and necrosis in HeLa cells via oxidative stress and glutathione depletion

in-vitro,

Cerv,

HeLa

TrxR↓, Auranofin (Au), an inhibitor of thioredoxin reductase, is a known anti‑cancer drug
AntiCan↑,
TumCG↓, Au inhibited the growth of HeLa cells with an IC50 of ~2 µM at 24 h.
Apoptosis↑, This agent induced apoptosis and necrosis, accompanied by the cleavage of poly (ADP‑ribose) polymerase and loss of mitochondrial membrane potential.
necrosis↑,
cl‑PARP↑,
MMP↓,
ROS↑, With respect to the levels of ROS and GSH, Au increased intracellular O2•- in the HeLa cells and induced GSH depletion.
GSH↓,
eff↓, The antioxidant, N‑acetyl cysteine, not only attenuated apoptosis and necrosis in the Au‑treated HeLa cells, but also decreased the levels of O2•- and GSH depletion in the cells.

4584-

AgNPs,

Silver Nanoparticles Synthesized Using Carica papaya Leaf Extract (AgNPs-PLE) Causes Cell Cycle Arrest and Apoptosis in Human Prostate (DU145) Cancer Cells

in-vitro,

Pca,

DU145

selectivity↑, AgNPs-PLE when compared with AgNPs-citric acid or PLE showed better efficacy against cancer cells and was also relatively less toxic to normal cells.
ROS↑, ROS production was observed at earlier time points in presence of AgNPs-PLE, suggesting its role behind apoptosis in DU145 cells.
BAX↑, induction of Bax, cleaved caspase-3, and cleaved PARP proteins. G1-S phase cell cycle check point marker, cyclin D1 was down-regulated along with an increase in cip1/p21 and kip1/p27 tumor suppressor proteins by AgNPs-PLE.
cl‑Casp3↑,
p‑PARP↑,
TumCCA↑,
cycD1/CCND1↓,
p27↑,
P21↑,
AntiCan↑, These findings suggest the anti-cancer properties of AgNPs-PLE.

5356-

AL,

Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects

Review,

GC,

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

2655-

AL,

Allicin and Digestive System Cancers: From Chemical Structure to Its Therapeutic Opportunities

Review,

GC,

TGF-β↓, Allicin can reduce the expression of TGF-2 and its receptor after entering directly into gastric cancer cell
cycD1/CCND1↓, followed by not only downexpression of cyclinD1, cyclinE, and cyclin-dependent kinase (CDK),
cycE/CCNE↓,
CDK1↓, cyclin-dependent kinase (CDK)
DNAdam↑, but also causing DNA damage and generating ROS
ROS↑,
BAX↑, Allicin increases the levels of Bax (proapoptotic protein), Bcl-2 (antiapoptotic protein), and JNK
JNK↑,
MMP↓, through reduction in outer mitochondrial membrane potential
p38↑, allicin induces p38 mitogen that could induce the protein kinase (MAPK) and then increase the expression of Fas binding to Fas ligand (Fas L) and finally activate death pathway through activation of cyt C and caspase-8.
MAPK↑,
Fas↑,
Cyt‑c↑,
Casp8↑,
PARP↑, allicin makes caspase-dependent apoptosis through elevating PARP, caspase-3 and caspase-9, which are mediated by enhanced discharging of mitochondria cyt C to the cytosol.
Casp3↑,
Casp9↑,
Ca+2↑, allicin induces apoptosis via increasing the amounts of free Ca2+, ER stress.
ER Stress↑,
P21↑, generating ROS to produce p21 and phospho-p53 (Ser15).
CDK2↓, Then p21 suppressed the CDK-4/6/cyclinD complex, P21-PCNA, P21-CDK2, and subsequently reduced cdk1/cyclinB1 complex for G2/M phase cell cycle arrest
CDK6↑,
TumCCA↑,
CDK4↓, Then p21 suppressed the CDK-4/6/cyclinD complex

233-

AL,

5-FU,

Allicin sensitizes hepatocellular cancer cells to anti-tumor activity of 5-fluorouracil through ROS-mediated mitochondrial pathway

in-vivo,

Liver,

 5 mg/kg/d; every two days for 3 weeks

 nude mide

ROS↑,
MMP↓,
Casp3↑, activated
PARP↑, increase of activated caspase-3 and PARP
Bcl-2↓,

1548-

Api,

A comprehensive view on the apigenin impact on colorectal cancer: Focusing on cellular and molecular mechanisms

Review,

Colon,

*BioAv↓, Apigenin is not easily absorbed orally because of its low water solubility, which is only 2.16 g/mL
*Half-Life∅, Apigenin is slowly absorbed and eliminated from the body, as evidenced by its half‐life of 91.8 h in the blood
selectivity↑, selective anticancer effects and effective cell cytotoxic activity while exhibiting negligible toxicity to ordinary cells
*toxicity↓, intentional consumption in higher doses, as the toxicity hazard is low
Wnt/(β-catenin)↓, inhibiting the Wnt/β‐catenin
P53↑,
P21↑,
PI3K↓,
Akt↓,
mTOR↓,
TumCCA↑, G2/M
TumCI↓,
TumCMig↓,
STAT3↓, apigenin can activate p53, which improves catalase and inhibits STAT3,
PKM2↓,
EMT↓, reversing increases in epithelial–mesenchymal transition (EMT)
cl‑PARP↑, apigenin increases the cleavage of poly‐(ADP‐ribose) polymerase (PARP) and rapidly enhances caspase‐3 activity,
Casp3↑,
Bax:Bcl2↑,
VEGF↓, apigenin suppresses VEGF transcription
Hif1a↓, decrease in hypoxia‐inducible factor 1‐alpha (HIF‐1α
Dose∅, effectiveness of apigenin (200 and 300 mg/kg) in treating CC was evaluated by establishing xenografts on Balb/c nude mice.
GLUT1↓, Apigenin has been found to inhibit GLUT1 activity and glucose uptake in human pancreatic cancer cells
GlucoseCon↓,

1536-

Api,

Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells

in-vitro,

MM,

MSTO-211H

0, 10, 30, and 50 µM) of apigenin for 48 h and 72 h

in-vitro,

MM,

H2452

tumCV↓,
ROS↑, increase in intracellular reactive oxygen species (ROS)
MMP↓, caused the loss of mitochondrial membrane potential (ΔΨm)
ATP↓, ATP depletion
Apoptosis↑,
Necroptosis↑,
DNAdam↑,
TumCCA↑, delay at the G2/M phase of cell cycle
Casp3↑,
cl‑PARP↑,
MLKL↑,
p‑RIP3↑,
Bax:Bcl2↑,
eff↓, ATP supplementation restored cell viability and levels of DNA damage-, apoptosis- and necroptosis-related proteins that apigenin caused.
eff↓, N-acetylcysteine reduced ROS production and improved ΔΨm loss and cell death that were caused by apigenin.

1563-

Api,

MET,

Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells

in-vitro,

Nor,

HDFa

metformin (5 mM), apigenin (1 or 20 µM),

in-vitro,

PC,

AsPC-1

in-vitro,

PC,

MIA PaCa-2

in-vitro,

Pca,

DU145

in-vitro,

Pca,

LNCaP

in-vivo,

NA,

mice

selectivity↑, Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts.
selectivity↑, Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells
selectivity↓, Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells
ROS↑,
eff↑, Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect.
tumCV↓,
MMP↓, Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells
Dose∅, co-treatment with metformin (0.05, 0.5 or 5 mM) and apigenin (20 µM) dramatically increased cellular ROS levels in AsPC-1 cells
eff↓, NAC blocked the metformin/apigenin co-treatment-induced cell death in AsPC-1 cells
DNAdam↑, Combination of metformin and apigenin leads to DNA damage-induced apoptosis, autophagy and necroptosis in AsPC-1 cells but not in HDF cells
Apoptosis↑,
TumAuto↑,
Necroptosis↑,
p‑P53↑, p-p53, Bim, Bid, Bax, cleaved PARP, caspase 3, caspase 8, and caspase 9 were also significantly increased by combination of metformin and apigenin in AsPC-1
BIM↑,
BAX↑,
p‑PARP↑,
Casp3↑,
Casp8↑,
Casp9↑,
Cyt‑c↑, Cytochrome C was also released from mitochondria in AsPC-1 cell
Bcl-2↓,
AIF↑, Interestingly, autophagy-related proteins (AIF, P62 and LC3B) and necroptosis-related proteins (MLKL, p-MLKL, RIP3 and p-RIP3) were also increased by combination of metformin and apigenin
p62↑,
LC3B↑,
MLKL↑,
p‑MLKL↓,
RIP3↑,
p‑RIP3↑,
TumCG↑, in vivo
TumW↓, metformin (125 mg/kg) or apigenin (40 mg/kg) caused a reduction of tumor size compared to the control group (Fig. 7D). However, oral administration of combination of metformin and apigenin decreased tumor weight profoundly

2639-

Api,

Plant flavone apigenin: An emerging anticancer agent

Review,

Var,

*antiOx↑, Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties
*Inflam↓,
AntiCan↑,
ChemoSen↑, Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers.
BioEnh↑, Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies.
chemoPv↑, apigenin highlighting its potential activity as a chemopreventive and therapeutic agent.
IL6↓, In taxol-resistant ovarian cancer cells, apigenin caused down regulation of TAM family of tyrosine kinase receptors and also caused inhibition of IL-6/STAT3 axis, thereby attenuating proliferation.
STAT3↓,
NF-kB↓, apigenin treatment effectively inhibited NF-κB activation, scavenged free radicals, and stimulated MUC-2 secretion
IL8↓, interleukin (IL)-6, and IL-8
eff↝, The anti-proliferative effects of apigenin was significantly higher in breast cancer cells over-expressing HER2/neu but was much less efficacious in restricting the growth of cell lines expressing HER2/neu at basal levels
Akt↓, Apigenin interferes in the cell survival pathway by inhibiting Akt function by directly blocking PI3K activity
PI3K↓,
HER2/EBBR2↓, apigenin administration led to the depletion of HER2/neu protein in vivo
cycD1/CCND1↓, Apigenin treatment in breast cancer cells also results in decreased expression of cyclin D1, D3, and cdk4 and increased quantities of p27 protein
CycD3↓,
p27↑,
FOXO3↑, In triple-negative breast cancer cells, apigenin induces apoptosis by inhibiting the PI3K/Akt pathway thereby increasing FOXO3a expression
STAT3↓, In addition, apigenin also down-regulated STAT3 target genes MMP-2, MMP-9, VEGF and Twist1, which are involved in cell migration and invasion of breast cancer cells [
MMP2↓,
MMP9↓,
VEGF↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
Twist↓,
MMP↓, Apigenin treatment of HGC-27 and SGC-7901 gastric cancer cells resulted in the inhibition of proliferation followed by mitochondrial depolarization resulting in apoptosis
ROS↑, Further studies revealed apigenin-induced apoptosis in hepatoma tumor cells by utilizing ROS generated through the activation of the NADPH oxidase
NADPH↑,
NRF2↓, Apigenin significantly sensitized doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increased the intracellular concentration of ADM by reducing Nrf2-
SOD↓, In human cervical epithelial carcinoma HeLa cells combination of apigenin and paclitaxel significantly increased inhibition of cell proliferation, suppressing the activity of SOD, inducing ROS accumulation leading to apoptosis by activation of caspas
COX2↓, melanoma skin cancer model where apigenin inhibited COX-2 that promotes proliferation and tumorigenesis
p38↑, Additionally, it was shown that apigenin treatment in a late phase involves the activation of p38 and PKCδ to modulate Hsp27, thus leading to apoptosis
Telomerase↓, apigenin inhibits cell growth and diminishes telomerase activity in human-derived leukemia cells
HDAC↓, demonstrated the role of apigenin as a histone deacetylase inhibitor. As such, apigenin acts on HDAC1 and HDAC3
HDAC1↓,
HDAC3↓,
Hif1a↓, Apigenin acts on the HIF-1 binding site, which decreases HIF-1α, but not the HIF-1β subunit, thereby inhibiting VEGF.
angioG↓, Moreover, apigenin was found to inhibit angiogenesis, as suggested by decreased HIF-1α and VEGF expression in cancer cells
uPA↓, Furthermore, apigenin intake resulted in marked inhibition of p-Akt, p-ERK1/2, VEGF, uPA, MMP-2 and MMP-9, corresponding with tumor growth and metastasis inhibition in TRAMP mice
Ca+2↑, Neuroblastoma SH-SY5Y cells treated with apigenin led to induction of apoptosis, accompanied by higher levels of intracellular free [Ca(2+)] and shift in Bax:Bcl-2 ratio in favor of apoptosis, cytochrome c release, followed by activation casp-9, 12
Bax:Bcl2↑,
Cyt‑c↑,
Casp9↑,
Casp12↑,
Casp3↑, Apigenin also augmented caspase-3 activity and PARP cleavage
cl‑PARP↑,
E-cadherin↑, Apigenin treatment resulted in higher levels of E-cadherin and reduced levels of nuclear β-catenin, c-Myc, and cyclin D1 in the prostates of TRAMP mice.
β-catenin/ZEB1↓,
cMyc↓,
CDK4↓, apigenin exposure led to decreased levels of cell cycle regulatory proteins including cyclin D1, D2 and E and their regulatory partners CDK2, 4, and 6
CDK2↓,
CDK6↓,
IGF-1↓, A reduction in the IGF-1 and increase in IGFBP-3 levels in the serum and the dorsolateral prostate was observed in apigenin-treated mice.
CK2↓, benefits of apigenin as a CK2 inhibitor in the treatment of human cervical cancer by targeting cancer stem cells
CSCs↓,
FAK↓, Apigenin inhibited the tobacco-derived carcinogen-mediated cell proliferation and migration involving the β-AR and its downstream signals FAK and ERK activation
Gli↓, Apigenin inhibited the self-renewal capacity of SKOV3 sphere-forming cells (SFC) by downregulating Gli1 regulated by CK2α
GLUT1↓, Apigenin induces apoptosis and slows cell growth through metabolic and oxidative stress as a consequence of the down-regulation of glucose transporter 1 (GLUT1).

2640-

Api,

Apigenin: A Promising Molecule for Cancer Prevention

Review,

Var,

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↑,

586-

Api,

5-FU,

5-Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential (ΔΨm)-mediated apoptosis in hepatocellular carcinoma

in-vivo,

HCC,

4 umol/L

20mg/kg/5x/wk/3wks

ROS↑,
MMP↓,
Bcl-2↓,
Casp3↑,
PARP↑,

176-

Api,

Induction of caspase-dependent extrinsic apoptosis by apigenin through inhibition of signal transducer and activator of transcription 3 (STAT3) signalling in HER2-overexpressing BT-474 breast cancer cells

in-vitro,

BC,

BT474

 0-100 uM 72hrs

cl‑Casp8↑, apigenin up-regulated the levels of cleaved caspase-8 and caspase-3, and induced the cleavage of PARP in BT-474 cells
cl‑Casp3↑,
p‑JAK1↓, apigenin reduced the expression of p-STAT3 as well as p-JAK1 and p-JAK2 (upstream kinases of STAT3)
p‑JAK2↓,
p‑STAT3↓,
P53↑,
VEGF↓, pigenin also reduced the level of VEGF
Hif1a↓, apigenin suppressed the expression of p-STAT3 and HIF-1α that was up-regulated by CoCl2 (hypoxia mimic)
MMP9↓,
TumCG↓, Apigenin suppresses the growth of BT-474 cells
TumCCA↑, The growth-suppressive activity of apigenin is accompanied by an increase in the sub-G 0 /G 1 apoptotic population in BT-474 cells
cl‑PARP↑,

243-

Api,

Apigenin Attenuates Melanoma Cell Migration by Inducing Anoikis through Integrin and Focal Adhesion Kinase Inhibition

in-vitro,

Melanoma,

A375

 50 uM

in-vitro,

Melanoma,

A2058

p‑FAK↓, Apigenin reduced integrin protein levels and inhibited the phosphorylation of focal adhesion kinase (FAK)
ERK↓, ERK1/2
Casp3↑,
PARP↑,
ITGA5↓, revealed that integrin subunits α4, α5, αV, and β3 were clearly downregulated in cell lysates of melanoma cells after apigenin treatment

178-

Api,

Autophagy inhibition enhances apigenin-induced apoptosis in human breast cancer cells

in-vivo,

BC,

MDA-MB-231

in-vitro,

BC,

T47D

Casp3↑,
cl‑PARP↑, cleavage
Bcl-2↓,
Bcl-xL↓,
BAX↑,

179-

Api,

Apigenin induces caspase-dependent apoptosis by inhibiting signal transducer and activator of transcription 3 signaling in HER2-overexpressing SKBR3 breast cancer cells

in-vitro,

BC,

SkBr3

cl‑Casp8↑, Apigenin induces apoptosis via caspase‑dependent pathways in SKBR3 cells.
cl‑Casp3↑,
VEGF↓,
TumCG↓, Apigenin suppresses the growth of SKBR3 cells.
TumCCA↑, Growth‑suppressive activity of apigenin is accompanied by an increase in the sub G0/G1 apoptotic population in SKBR3 cells.
cl‑PARP↑, induced PARP cleavage in SKBR3 cells
p‑STAT3↓, apigenin reduced the expression of p-STAT3 and p-JAK2 in SKBR3 cells.
p‑JAK2↓,

180-

Api,

Induction of caspase-dependent apoptosis by apigenin by inhibiting STAT3 signaling in HER2-overexpressing MDA-MB-453 breast cancer cells

in-vitro,

BC,

MDA-MB-231

 0-100 uM 72hrs

cl‑Casp8↑, cleaved
cl‑Casp3↑, cleaved
cl‑PARP↑, cleaved
BAX∅, failed to regulate
Bcl-2∅, failed to regulate
Bcl-xL∅, failed to regulate
p‑STAT3↓,
P53↑,
P21↑,
p‑JAK2↓, p-JAK2
VEGF↓,

206-

Api,

Inhibition of glutamine utilization sensitizes lung cancer cells to apigenin-induced apoptosis resulting from metabolic and oxidative stress

in-vitro,

Lung,

H1299

 20 uM

in-vitro,

Lung,

H460

in-vitro,

Lung,

A549

 40 uM

in-vitro,

CRC,

HCT116

in-vitro,

Melanoma,

A375

in-vitro,

Lung,

H2030

in-vitro,

CRC,

SW480

Glycolysis↓, glucose consumption, lactate production, and ATP production were all strongly decreased by apigenin
lactateProd↓,
PGK1↓,
ALDOA↓,
GLUT1↓, Apigenin reduces GLUT1 expression levels.
ENO1↓,
ATP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑, cleavage
PI3K/Akt↓,
HK1↓, HK1, HK2
HK2↓,
ROS↑, Apigenin causes oxidative stress leading to apoptosis. Because apoptotic signal transduction cascades involving caspase-9, -3 and PARP cleavage can be activated by increased ROS levels
Apoptosis↑,
eff↓, Cancer cells expressing high levels of GLUT1 are resistant to apigenin-induced apoptosis through metabolic compensation of glucose utilization.
NADPH↓, apigenin significantly decreased glucose utilization through suppression of GLUT1 expression, and consequently decreased NADPH production, which led to increased ROS levels.
PPP↓, inhibition of the PPP

270-

Api,

Apigenin induces apoptosis in human leukemia cells and exhibits anti-leukemic activity in vivo via inactivation of Akt and activation of JNK

in-vivo,

AML,

U937

 20-40 uM (12/24h)

Akt↓, nactivation of Akt and activation of JNK
JNK↑,
Mcl-1↓,
cl‑Bcl-2↓, cleavage
Casp3↑,
Casp7↑,
Casp9↑,
cl‑PARP↑, cleaved
mTOR↓,
GSK‐3β↓,

268-

Api,

Induction of apoptosis by apigenin and related flavonoids through cytochrome c release and activation of caspase-9 and caspase-3 in leukaemia HL-60 cells

in-vitro,

AML,

HL-60

 60 uM

Casp3↑,
PARP↑,

173-

Api,

Apigenin-induced apoptosis is enhanced by inhibition of autophagy formation in HCT116 human colon cancer cells

in-vitro,

Colon,

HCT116

 25, 50 uM

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↓,

242-

Api,

Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells

in-vitro,

Melanoma,

A375

 (40, 80, 120, 160, 200, 240 and 280 µM) for (24, 48, 72 and 96 h).

in-vitro,

Melanoma,

C8161

ERK↓,
PI3k/Akt/mTOR↓, Akt/mTOR
Casp3↑, cleaved
PARP↑, cleaved
p‑mTOR↓,
p‑Akt↓,

3383-

ART/DHA,

Dihydroartemisinin: A Potential Natural Anticancer Drug

Review,

Var,

TumCP↓, DHA exerts anticancer effects through various molecular mechanisms, such as inhibiting proliferation, inducing apoptosis, inhibiting tumor metastasis and angiogenesis, promoting immune function, inducing autophagy and endoplasmic reticulum (ER) stres
Apoptosis↑,
TumMeta↓,
angioG↓,
TumAuto↑,
ER Stress↑,
ROS↑, DHA could increase the level of ROS in cells, thereby exerting a cytotoxic effect in cancer cells
Ca+2↑, activation of Ca2+ and p38 was also observed in DHA-induced apoptosis of PC14 lung cancer cells
p38↑,
HSP70/HSPA5↓, down-regulation of heat-shock protein 70 (HSP70) might participate in the apoptosis of PC3 prostate cancer cells induced by DHA
PPARγ↑, DHA inhibited the growth of colon tumor by inducing apoptosis and increasing the expression of peroxisome proliferator-activated receptor γ (PPARγ)
GLUT1↓, DHA was shown to inhibit the activity of glucose transporter-1 (GLUT1) and glycolytic pathway by inhibiting phosphatidyl-inositol-3-kinase (PI3K)/AKT pathway and downregulating the expression of hypoxia inducible factor-1α (HIF-1α)
Glycolysis↓, Inhibited glycolysis
PI3K↓,
Akt↓,
Hif1a↓,
PKM2↓, DHA could inhibit the expression of PKM2 as well as inhibit lactic acid production and glucose uptake, thereby promoting the apoptosis of esophageal cancer cells
lactateProd↓,
GlucoseCon↓,
EMT↓, regulating the EMT-related genes (Slug, ZEB1, ZEB2 and Twist)
Slug↓, Downregulated Slug, ZEB1, ZEB2 and Twist in mRNA level
Zeb1↓,
ZEB2↓,
Twist↓,
Snail?, downregulated the expression of Snail and PI3K/AKT signaling pathway, thereby inhibiting metastasis
CAFs/TAFs↓, DHA suppressed the activation of cancer-associated fibroblasts (CAFs) and mouse cancer-associated fibroblasts (L-929-CAFs) by inhibiting transforming growth factor-β (TGF-β signaling
TGF-β↓,
p‑STAT3↓, blocking the phosphorylation of STAT3 and polarization of M2 macrophages
M2 MC↓,
uPA↓, DHA could inhibit the growth and migration of breast cancer cells by inhibiting the expression of uPA
HH↓, via inhibiting the hedgehog signaling pathway
AXL↓, DHA acted as an Axl inhibitor in prostate cancer, blocking the expression of Axl through the miR-34a/miR-7/JARID2 pathway, thereby inhibiting the proliferation, migration and invasion of prostate cancer cells.
VEGFR2↓, inhibition of VEGFR2-mediated angiogenesis
JNK↑, JNK pathway activated and Beclin 1 expression upregulated.
Beclin-1↑,
GRP78/BiP↑, Glucose regulatory protein 78 (GRP78, an ER stress-related molecule) was upregulated after DHA treatment.
eff↑, results demonstrated that DHA-induced ER stress required iron
eff↑, DHA was used in combination with PDGFRα inhibitors (sunitinib and sorafenib), it could sensitize ovarian cancer cells to PDGFR inhibitors and achieved effective therapeutic efficacy
eff↑, DHA combined with 2DG (a glycolysis inhibitor) synergistically induced apoptosis through both exogenous and endogenous apoptotic pathways
eff↑, histone deacetylase inhibitors (HDACis) enhanced the anti-tumor effect of DHA by inducing apoptosis.
eff↑, DHA enhanced PDT-induced cell growth inhibition and apoptosis, increased the sensitivity of esophageal cancer cells to PDT by inhibiting the NF-κB/HIF-1α/VEGF pathway
eff↑, DHA was added to magnetic nanoparticles (MNP), and the MNP-DHA has shown an effect in the treatment of intractable breast cancer
IL4↓, downregulated IL-4;
DR5↑, Upregulated DR5 in protein, Increased DR5 promoter activity
Cyt‑c↑, Released cytochrome c from the mitochondria to the cytosol
Fas↑, Upregulated fas, FADD, Bax, cleaved-PARP
FADD↑,
cl‑PARP↑,
cycE/CCNE↓, Downregulated Bcl-2, Bcl-xL, procaspase-3, Cyclin E, CDK2 and CDK4
CDK2↓,
CDK4↓,
Mcl-1↓, Downregulated Mcl-1
Ki-67↓, Downregulated Ki-67 and Bcl-2
Bcl-2↓,
CDK6↓, Downregulated of Cyclin E, CDK2, CDK4 and CDK6
VEGF↓, Downregulated VEGF, COX-2 and MMP-9
COX2↓,
MMP9↓,

2323-

ART/DHA,

Dihydroartemisinin represses esophageal cancer glycolysis by down-regulating pyruvate kinase M2

in-vitro,

ESCC,

Eca109

10, 40, 80, 120 umol/L)

in-vitro,

ESCC,

EC9706

PKM2↓, DHA treatment cells, PKM2 was down-regulated and lactate product and glucose uptake were inhibited.
lactateProd↓,
GlucoseCon↓,
cycD1/CCND1↓, DHA treatment resulted in the down-regulation of the expression of PKM2, cyclin D1, Bcl-2, matrix metalloproteinase-2 (MMP2), vascular endothelial growth factor A (VEGF-A) and the up-regulation of caspase 3, cleaved-PARP and Bax
Bcl-2↓,
MMP2↓,
VEGF↓,
Casp3↑,
cl‑PARP↑,
BAX↑,
DNAdam↑, The specific mechanism of DHA towards cancer cells include inducing DNA damage and repair (Li et al., 2008), oxidative stress response by reactive oxygen species
ROS↑,

3155-

Ash,

Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera

Review,

Var,

Half-Life↝, The pharmacokinetic study demonstrates that a dose of 4 mg/kg in mice results in 2 Î¼M concentration in plasma (with a half-life of 1.3 h, in the breast cancer model of mice),
Inflam↓, WA has many biological activities: anti-inflammatory (Dubey et al. 2018), immunomodulatory (Davis and Girija 2000), antistress (Singh et al. 2016), antioxidant (Sumathi et al. 2007) and anti-angiogenesis
antiOx↓,
angioG↓,
ROS↑, WA induces oxidative stress (ROS) determining mitochondrial dysfunction as well as apoptosis in leukaemia cells
BAX↑, withaferin mediates apoptosis by ROS generation and activation of Bax/Bak.
Bak↑,
E6↓, The results of the study show that withaferin treatment downregulates the HPV E6 and E7 oncoprotein and induces accumulation of p53 result in the activation of various apoptotic markers (e.g. Bcl2, Bax, caspase-3 and cleaved PARP).
E7↓,
P53↑,
Casp3↑,
cl‑PARP↑,
STAT3↓, WA treatment also decreases the level of STAT3
eff↑, This study concludes that combination of DOX with WA can reduce the doses and side effects of the treatment which gives valuable possibilities for future research.
HSP90↓, by inhibiting the HSP90
TGF-β↓, WA inhibited TGFÎ²1 and TNFÎ±- induced EMT;
TNF-α↓,
EMT↑,
mTOR↓, by downregulation of mTOR/STAT3 signalling.
NOTCH1↓, WA showed inhibition of pro-survival signalling markers (Notch1, pAKT and NFÎºB)
p‑Akt↓,
NF-kB↓,
Dose↝, WA dose escalation sets consisted of 72, 108, 144 and 216 mg, fractioned in 2-4 doses/day.

3160-

Ash,

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Review,

Var,

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

3167-

Ash,

Withaferin A Inhibits the Proteasome Activity in Mesothelioma In Vitro and In Vivo

in-vitro,

MM,

H226

0-5uM

TumCP↓, WA inhibits MPM cell proliferation
cMyc↓, Among the genes that were down-regulated included cell growth and metastasis-promoting oncogenes c-myc, c-fos, c-jun, while tissue inhibitor of metallopeptidases (TIMP)-2 was significantly upregulated
cFos↓,
cJun↓,
TIMP2↑,
Vim↓, WA exposure caused reduced levels of vimentin at 24 h of treatment.
ROS↑, WA treatment generated reactive oxygen species (ROS), causing cell death in HL-60 cells
BAX↑, Consistent with these findings, we found that WA treatments increased pro-apoptotic protein Bax and NF-κB inhibitory protein IκB-α in the patient derived MPM cells.
IKKα↑,
Casp3↑, Indeed, WA treatment induced caspase-3 activation, PARP cleavage,
cl‑PARP↑,

1369-

Ash,

Withaferin A inhibits cell proliferation of U266B1 and IM-9 human myeloma cells by inducing intrinsic apoptosis

in-vitro,

Melanoma,

U266

9 μM

tumCV↓,
Apoptosis↑,
BAX↑,
Cyt‑c↑,
Bcl-2↓,
cl‑PARP↑,
cl‑Casp3↑,
cl‑Casp9↑,
ROS↑,
eff↓, treatment of the U266B1 and IM-9 with ascorbic acid (antioxidant) could prevent the withaferin A mediated ROS production and the withaferin A induced antiproliferative effects.

1371-

Ash,

Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine

in-vitro,

AML,

HL-60

ROS↑,
MMP↓,
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
eff↓, N-acetyl-cysteine rescued all these events suggesting thereby a pro-oxidant effect of withaferinA.

1360-

Ash,

immuno,

Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer

in-vitro,

Lung,

H1650

in-vitro,

Lung,

A549

in-vitro,

CRC,

HCT116

in-vitro,

BC,

MDA-MB-231

in-vivo,

NA,

mice

PD-L1↑,
eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
ROS↑,
ER Stress↑,
Apoptosis↑,
BAX↑,
Bak↑,
BAD↑,
Bcl-2↓,
XIAP↓,
survivin↓,
cl‑PARP↑,
CHOP↑,
p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
ICD↑,
eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo

1364-

Ash,

Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

in-vitro,

Bladder,

J82

cl‑Casp3↑,
cl‑Casp8↑,
cl‑Casp9↑,
cl‑PARP↑,
ROS↑,
MMP↓,
DNAdam↑,
eff↓, ROS scavenger N-acetylcysteine reverts all tested WFA-modulating effects.

5449-

ATV,

Pleiotropic effects of statins: A focus on cancer

NA,

Var,

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

5362-

AV,

Anti-cancer effects of aloe-emodin: a systematic review

Review,

Var,

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

5248-

Ba,

BA,

doxoR,

Baicalin and Baicalein Enhance Cytotoxicity, Proapoptotic Activity, and Genotoxicity of Doxorubicin and Docetaxel in MCF-7 Breast Cancer Cells

in-vitro,

BC,

MCF-7

in-vitro,

Nor,

HUVECs

toxicity↝, We have found that baicalin and baicalein demonstrated cytotoxicity towards both cell lines, with more potent effects observed in baicalein.
ChemoSen↑, Both flavonoids, baicalin (167 µmol/L) and baicalein (95 µmol/L), synergistically enhanced the cytotoxic, proapoptotic, and genotoxic activity of doxorubicin and docetaxel in breast cancer cells.
selectivity↑, Surprisingly, low concentrations of baicalin and baicalein had a greater effect on MCF-7 viability. A
Apoptosis↑, Induction of Apoptosis and Necrosis by Baicalin and Baicalein Used alone and in Combination with Anticancer Drugs
necrosis↑,
MMP↓, After treatment with baicalin and baicalein at high concentrations (IC50), the ΔΨm of cancer cells was diminished to 30% of the control value
DNAdam↑, DNA Damage Induced by Baicalin and Baicalein Used Alone and in Combination with Anticancer Drugs
cl‑PARP↑, PARP Cleavage Induced by Baicalin and Baicalein Used Alone and in Combination with Anticancer Drugs
MRP1↓, Moreover, baicalin and baicalein reduced cisplatin resistance by inhibiting the expression of genes involved in drug resistance, such as MRP1 [30] and Bcl-2, and via the Akt/mTOR and Nrf2/Keap 1 pathway [26].
Bcl-2↓,
hepatoP↑, baicalin and baicalein can also help decrease the side effects of cisplatin treatment by protecting the liver from damage [31]
cardioP↑, Similar to baicalein, baicalin also significantly protects against doxorubicin’s cardiotoxicity.
BioAv↝, This is because baicalein has a smaller size and high lipophilicity, contributing to fast absorption and an improved ability to penetrate cells [60].

5250-

Ba,

Exploring baicalein: A natural flavonoid for enhancing cancer prevention and treatment

Review,

Var,

Apoptosis↑, Baicalein is thought to prevent cancer progression by inducing apoptosis, autophagy, and genome instability, and its ability to promote chemo-potentiation, anti-metastatic effects, and regulate specific signalling molecules and transcription factors.
TumAuto↑,
DNAdam↑,
*antiOx↑, Baicalein has already been proven to be a radical scavenger that acts as an antioxidant [14,15
Inflam↓, it can also reduce inflammation [16] and act as an E2 prostaglandin inhibitor [17].
PGE2↓,
TumCCA↑, Baicalein properties prevent cell proliferation, induce apoptosis, autophagy, cell cycle arrest, cancer cell migration and invasion, and decrease angiogenesis [18,19].
TumCMig↓,
TumCI↓,
angioG↓,
selectivity↑, Furthermore, some studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells.
ChemoSen↑, the current review emphasises baicaleins' synergistic potential with other chemotherapeutic agents
HIF-1↓, baicalein against ovarian cancer by demonstrating that it can limit tumour cell viability by downregulating the expression of cancer-promoting genes such as HIF-1, cMyc, NFkB, and VEGF
cMyc↓,
NF-kB↓,
VEGF↓,
P53↑, Baicalein has been shown to activate p53, a tumour suppressor protein that regulates cell growth and division [26].
MMP2↓, anticancer properties of baicalein are mediated through various molecular mechanisms, including inhibition of MMP-2;
CSCs↓, inhibition of cancer stem cells
Bcl-xL↓, after bladder cancer cells were treated with baicalein, the expression of antiapoptotic genes (Bcl2, Bcl-xL, XIAP, and survivin) was reduced, and cell viability was decreased [38].
XIAP↓,
survivin↓,
tumCV↓,
Casp3↑, upregulating the expression of caspase-3 and caspase-8 and decreased the BCL-2/BAX ratio [16]
Casp8↑,
Bax:Bcl2↑,
Akt↓, in lung cancer cells, apoptosis was induced through the downregulation of the Akt/mTOR signalling pathway [25].
mTOR↓,
PCNA↓, baicalein treatment promoted apoptosis in mice with U87 gliomas by downregulating PCNA expression, enhancing the expression of caspase-3 and caspase-9 and improving the Bax/Bcl-2 ratio
MMP↓, baicalein treatment of lung cancer cells caused a collapse of the mitochondrial membrane potential (MMP), an increase in ROS generation, and enhanced PARP, caspase 3, and caspase 9 cleavage,
ROS↑,
PARP↑,
Casp9↑,
BioAv↑, Baicalein has been found to enhance the cytotoxicity and bioavailability of certain cancer therapy drugs when combined [85]
eff↑, combination of baicalein with silymarin differentially decreased the viability of HepG2 cells, enhanced the proportion of cells in the G0/G1 phase, upregulated tumour suppressors such as Rb and p53 and CDK inhibitors, and downregulated cyclin D1, cyc
P-gp↓, By inhibiting P-glycoprotein (P-gp), baicalein can increase the accumulation of chemotherapeutic drugs within cancer cells [21]
BioAv↑, selenium–baicalein nanoparticles as a targeted therapeutic strategy for NSCLC. This strategy significantly improves the bioavailability of baicalein through several mechanisms.
selectivity↑, ome studies have suggested that baicalein has a lower toxicity on normal cells than cancer cells, indicating some selectivity for cancer cells

1528-

Ba,

Inhibiting reactive oxygen species-dependent autophagy enhanced baicalein-induced apoptosis in oral squamous cell carcinoma

in-vitro,

OS,

CAL27

1-100uM

Apoptosis↑,
ROS↑, baicalein triggered reactive oxygen species (ROS) generation in Cal27 cells
eff↓, Furthermore, N-acetyl-cysteine, a ROS scavenger, abrogated the effects of baicalein on ROS-dependent autophagy.
TumAuto↑, baicalein increased autophagy through the promotion of ROS signaling pathways in OSCC.
cl‑PARP↑,
Bax:Bcl2↑,
Beclin-1↑, enhancement of Beclin-1 and degradation of p62
p62↓,

1526-

Ba,

Baicalein induces apoptosis through ROS-mediated mitochondrial dysfunction pathway in HL-60 cells

in-vitro,

AML,

HL-60

25uM

Apoptosis↑, 100 microM for 6 h
cl‑PARP↑,
DNAdam↑, DNA fragmentation.
cl‑BID↑,
Cyt‑c↑, cytochrome c release from mitochondria into cytosol
Casp3↑,
Casp8↑,
Casp9?,
H2O2↑, baicalein caused elevation of intracellular hydrogen peroxide level
ROS↑, apoptotic death program through reactive oxygen species (ROS)-mediated mitochondrial dysfunction pathway

1525-

Ba,

almon,

Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway

in-vitro,

Lung,

H1975

in-vivo,

Lung,

mice

eff↑, Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation
TumCP↓,
Apoptosis↑,
cl‑Casp3↑,
cl‑PARP↑,
cl‑Casp9↑,
p‑PI3K↓, combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.
p‑Akt↓,
ROS↑, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS)
eff↓, preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction

1524-

Ba,

Baicalein Induces Caspase‐dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells

in-vitro,

Lung,

A549

25–125 uM, 24hr

100uM

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

2476-

Ba,

Baicalein Induces Caspase-dependent Apoptosis Associated with the Generation of ROS and the Activation of AMPK in Human Lung Carcinoma A549 Cells

in-vitro,

Lung,

A549

0-125uM

TumCG↓, baicalein-induced growth inhibition was associated with the induction of apoptosis in human lung carcinoma A549 cells.
Apoptosis↑,
DR5↑, Baicalein stimulated the expression of DR5, FasL, and FADD, and activated caspase-8 by reducing the levels of FLIPs (FLICE-inhibitory proteins).
FasL↑,
FADD↑,
Casp8↑,
cFLIP↓,
Casp9↑, activation of caspase-9 and -3, and cleavage of poly(ADP-ribose) polymerase
Casp3↑,
cl‑PARP↑,
MMP↓, Additionally, baicalein caused a mitochondrial membrane potential (MMP), the truncation of Bid, and the translocation of pro-apoptotic Bax to the mitochondria, thereby inducing the release of cytochrome c into the cytosol.
BID↑,
BAX↑,
Cyt‑c↑,
ROS↑, In turn, baicalein increased the generation of reactive oxygen species (ROS)
eff↓, however, an ROS scavenger, N-acetylcysteine, notably attenuated baicalein-mediated loss of MMP and activation of caspases.
AMPK↑, connected with ROS generation and AMPK activation.

2474-

Ba,

Anticancer properties of baicalein: a review

Review,

Var,

in-vitro,

Nor,

BV2

ROS⇅, Like other flavonoids, baicalein can be either anti-oxidant or pro-oxidant, depending on its metabolism and concentration.
ROS↑, It is reported that baicalein generated ROS, subsequently caused endoplasmic reticulum (ER) stress, activated Ca2+-dependent mitochondrial death pathway, finally triggered apoptosis
ER Stress↑,
Ca+2↑,
Apoptosis↑,
eff↑, Due to this, ROS production is a mechanism shared by all non-surgical therapeutic approaches for cancer, including chemotherapy, radiotherapy and photodynamic therapy
DR5↑, baicalein-induced ROS generation up-regulated DR5 expression and then activated the extrinsic apoptotic pathway in human prostate cancer cells
12LOX↓, Baicalein is known as a 12-LOX inhibitor.
Cyt‑c↑, It markedly induced the release of Cytochrome c from mitochondria into the cytosol and activated Caspase-9, Caspase-7, and Caspase-3, concomitant with cleavage of the Caspase-3 substrate poly(ADP-ribose) polymerase
Casp7↑,
Casp9↑,
Casp3↑,
cl‑PARP↑,
TumCCA↑, Baicalein induces G1/S arrest due to increased Cyclin E expression, a major factor in the regulation of the G1/S checkpoint of the cell cycle, accompanied by reduced levels of Cdk 4 and Cyclin D1 in human lung squamous carcinoma (CH27) cells
cycE/CCNE↑,
CDK4↓,
cycD1/CCND1↓,
VEGF↓, In ovarian cancer cells, baicalein effectively lowered the protein level of VEGF, c-Myc, HIF-α, and NFκB
cMyc↓,
Hif1a↓,
NF-kB↓,
BioEnh↑, curcumin and high-dose (−)-epicatechin were demonstrated to subsequently increase the absorption of baicalein
BioEnh↑, Baicalein can increase the oral bioavailability of tamoxifen by inhibiting cytochrome P450 (CYP) 3A4-mediated metabolism of tamoxifen in the small intestine and/or liver,
P450↓,
*Hif1a↓, In BV2 microglia, baicalein suppressed expression of hypoxia-induced HIF-1α and hypoxia responsive genes, including inducible nitric oxide synthase (iNOS), COX-2, and VEGF, by inhibiting ROS and PI3K/Akt pathway (Hwang et al. 2008).
*iNOS↓,
*COX2↓,
*VEGF↓,
*ROS↓,
*PI3K↓,
*Akt↓,

2603-

Ba,

Baicalein inhibits prostate cancer cell growth and metastasis via the caveolin-1/AKT/mTOR pathway

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

TumCG↓, baicalein potently suppressed the growth and induced the apoptosis of DU145 and PC-3
Apoptosis↑,
Cav1↓, baicalein can suppress caveolin-1 and the phosphorylation of AKT and mTOR in a time- and dose-dependent manner
p‑Akt↓,
p‑mTOR↓,
Bax:Bcl2↑, revealed that the Bax/Bcl-2 ratio was increased after baicalein treatment in a dose-dependent manner
survivin↓, survivin was decreased, whereas the level of cleaved PARP was elevated.
cl‑PARP↑,
BioAv↓, Although low water solubility, fast oxidative degradation, and fast metabolism limit its pharmaceutical use in some degree, various methods have been used to overcome these issues of flavonoids

2600-

Ba,

Baicalein Induces Apoptosis and Autophagy via Endoplasmic Reticulum Stress in Hepatocellular Carcinoma Cells

in-vitro,

HCC,

SMMC-7721 cell

19.89uM 48h

in-vitro,

HCC,

Bel-7402

ER Stress↑, Baicalein induced apoptosis via endoplasmic reticulum (ER) stress
Bcl-2↓, possibly by downregulating prosurvival Bcl-2 family, increasing intracellular calcium, and activating JNK
Ca+2↑,
JNK↑,
CHOP↑, CHOP was the executor of cell death during baicalein-induced ER stress while eIF2α and IRE1α played protective roles.
Casp9↑, The results indicated that baicalein caused marked cleavage of caspase-9, caspase-3, and PARP dose- and time-dependently
Casp3↑,
PARP↑,
Apoptosis↑, these results demonstrated that baicalein promoted HCC cell death through inducing apoptosis.
UPR↑, Baicalein Induces ER Stress and Activates UPR Pathways

2296-

Ba,

The most recent progress of baicalein in its anti-neoplastic effects and mechanisms

Review,

Var,

CDK1↓, graphical abstract
Cyc↓,
p27↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

5539-

BBM,

Berbamine suppresses cell viability and induces apoptosis in colorectal cancer via activating p53-dependent apoptotic signaling pathway

vitro+vivo,

CRC,

SW480

tumCV↓, Berbamine suppressed the cell viability of CRC cells in concentration-dependent and time-dependent manners.
TumCCA↑, berbamine increased cell apoptotic rate and induced cell cycle arrest at G0/G1 phase.
MMP↓, Berbamine treatment also decreased the mitochondrial membrane potential in CRC cells.
P53↑, berbamine increased the protein levels of p53, caspase-3, caspase-9, Bax and poly ADP ribose polymerase, and decreased the protein levels of Bcl-2 in CRC cells.
Casp3↑,
Casp9↑,
BAX↑,
PARP↑,
Bcl-2↓,
TumVol↑, Tumor growth by grafted SW480 cells were significantly suppressed in berbamine group.

5553-

BBM,

A review on berbamine–a potential anticancer drug

Review,

Var,

P-gp↓, Treatment with berbamine decreased P-glycoprotein (P-gp) expression and down-regulated expression of MDR1 (multi-drug resistance1) and survivin mRNA in K562/A02 cells
MDR1↓,
survivin↓,
NF-kB↓, decrease expression of nuclear factor-B (NF-B), phosphoIB, IKK, and survivin.
TumCP↓, In a chronic myeloid leukemia cell line KU812, berbamine inhibited cell proliferation in a time- and dose-dependent manner, with IC50 values for treatments of 24, 48, and 72 h at 5.83, 3.43, and 0.75 μg/ml, respectively.
TumCCA↑, Berbamine induced cell cycle arrest at the G1 phase and also induced apoptosis.
Apoptosis↑,
SMAD3↑, The compound up-regulated transcriptions of Smad3 and p21, and increased protein levels of both total Smad3 and phosphorylated Smad3.
P21↑,
cycD1/CCND1↓, The protein levels of cyclin D1 and c-Myc were reduced.
cMyc↑,
Bcl-2↓, The levels of the anti-apoptotic proteins Bcl-2 and Bcl-xL were decreased, and the level of the pro-apoptotic protein Bax was increased.
Bcl-xL↓,
BAX↑,
CaMKII ↓, The compound has been shown to specifically bind to the ATP-binding pocket of calmodulin kinase (CAMK)II, inhibit its phosphorylation, and trigger apoptosis.
ChemoSen↑, Berbamine also significantly enhanced the activity of anticancer drugs like trichostatin A and celecoxib.
MMP2↓, EBB down-regulated the activities and mRNA levels of matrix metalloproteinases (MMP) 2 and 9, and up-regulated the mRNA levels of tissue inhibitor of metalloproteinases (TIMP) 1.
MMP9↓,
TIMP1↑,
cl‑Casp3↑, induction of apoptosis, including activation and cleavage of caspases 3, 8, 9 and PARP.
cl‑Casp9↑,
cl‑Casp8↑,
cl‑PARP↑,
IL6↓, BBD inhibited autocrine IL-6 production, and down-regulated membrane IL-6 receptor (IL-6R) expression.
ROS↑, Production of reactive oxygen species (ROS) was increased by BBMD3 in these cells.

2023-

BBR,

Berberine Induces Caspase-Independent Cell Death in Colon Tumor Cells through Activation of Apoptosis-Inducing Factor

in-vitro,

Colon,

0-100uM

in-vitro,

Nor,

YAMC

TumCD↑, Berberine decreased colon tumor colony formation in agar, and induced cell death and LDH release in a time- and concentration-dependent manner in IMCE cells.
*toxicity↓, In contrast, YAMC(normal) cells were not sensitive to berberine-induced cell death. less cytotoxic effects on normal colon epithelial cells.
selectivity↑, see figure 2
ROS↑, berberine-stimulated ROS production
*ROS∅, ROS production in a concentration-dependent manner only in IMCE cells, but not in YAMC cells. In YAMC cells, berberine did not induce ROS production
MMP↓, berberine induced mitochondrial depolarization in a concentration-dependent manner in IMCE cells, but not in YAMC cells
*MMP∅, but not in YAMC cells
PARP↑, Berberine Activation of PARP
BioAv↝, absorption of berberine by YAMC is lower than that by IMCE cells

1402-

BBR,

Berberine-induced apoptosis in human glioblastoma T98G cells is mediated by endoplasmic reticulum stress accompanying reactive oxygen species and mitochondrial dysfunction

in-vitro,

GBM,

T98G

tumCV↓,
ROS↑,
Ca+2↑,
ER Stress↑,
eff↓, administration of the antioxidants, N-acetylcysteine and glutathione, reversed berberine-induced apoptosis
Bax:Bcl2↑,
MMP↓,
Casp9↑,
Casp3↑,
cl‑PARP↑,

1404-

BBR,

Berberine-induced apoptosis in human prostate cancer cells is initiated by reactive oxygen species generation

in-vitro,

Pca,

PC3

Apoptosis↑,
*Apoptosis∅, not seen in non-neoplastic human prostate epithelial cells (PWR-1E)
MMP↓,
cl‑Casp3↑,
cl‑Casp9↑,
cl‑PARP↑,
ROS↑,
eff↓, Treatment of cells with allopurinol, an inhibitor of xanthine oxidase, inhibited berberine-induced oxidative stress in cancer cells.
Cyt‑c↑, release of cytochrome c

2691-

BBR,

Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells

in-vitro,

Oral,

tumCV↓, viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner.
DNAdam↑, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation.
Casp3↑, caspase-3 and -7 activation, and an increase in apoptosis were observed.
Casp7↑,
FasL↑, Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL
Casp8↑, triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP).
Casp9↑,
PARP↑,
BAX↑, Bax, Bad and Apaf-1 were also significantly upregulated by berberine.
BAD↑,
APAF1↑,
MMP2↓, We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK.
MMP9↓,
p‑p38↑, This suggests that berberine-induced activation of the p38 and ERK1/2 MAPK pathways is the principal pathway involved in the apoptosis mediated by berberine in KB cells.
ERK↑,
MAPK↑,

Showing Research Papers: 1 to 50 of 256
Page 1 of 6 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 256

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 2, NRF2↑, 1, Prx↑, 1, ROS↓, 1, ROS∅, 1, SOD2↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP∅, 1,

Cell Death ⓘ

Akt↓, 1, Apoptosis∅, 1, Casp3?, 1, iNOS↓, 1, MAPK↓, 1,

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,

Migration ⓘ

PKCδ↓, 1,

Angiogenesis & Vasculature ⓘ

Hif1a↓, 1, VEGF↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, Inflam↓, 2,

Drug Metabolism & Resistance ⓘ

BioAv↓, 1, Half-Life∅, 1,

Clinical Biomarkers ⓘ

GutMicro↑, 1,

Functional Outcomes ⓘ

chemoP↑, 1, toxicity↓, 3,
Total Targets: 23

Scientific Paper Hit Count for: PARP, poly ADP-ribose polymerase (PARP) cleavage

16 Apigenin (mainly Parsley)
14 Curcumin
13 Thymoquinone
12 Fisetin
11 Baicalein
11 Quercetin
10 Sulforaphane (mainly Broccoli)
8 Shikonin
7 Ashwagandha(Withaferin A)
7 Berberine
7 Capsaicin
7 EGCG (Epigallocatechin Gallate)
6 Boswellia (frankincense)
6 Carnosic acid
5 Honokiol
5 Piperlongumine
5 Silymarin (Milk Thistle) silibinin
4 Betulinic acid
4 Carvacrol
4 Chrysin
4 Citric Acid
4 Emodin
4 Garcinol
4 Phenethyl isothiocyanate
4 Resveratrol
4 Vitamin C (Ascorbic Acid)
3 Auranofin
3 Allicin (mainly Garlic)
3 Metformin
3 doxorubicin
3 Bufalin/Huachansu
3 Brucea javanica
3 Thymol-Thymus vulgaris
3 Docetaxel
3 Ellagic acid
3 Gambogic Acid
3 Magnetic Fields
3 Propolis -bee glue
3 Propyl gallate
2 5-fluorouracil
2 Artemisinin
2 Berbamine
2 temozolomide
2 brusatol
2 Radiotherapy/Radiation
2 Cisplatin
2 HydroxyTyrosol
2 Juglone
2 Luteolin
2 Lycopene
2 Magnolol
2 Nimbolide
2 Paclitaxel
2 Piperine
2 Selenite (Sodium)
2 Ursolic acid
2 Urolithin
1 Silver-NanoParticles
1 immunotherapy
1 Atorvastatin
1 Aloe anthraquinones
1 Baicalin
1 almonertinib
1 Bromelain
1 Butyrate
1 Sorafenib (brand name Nexavar)
1 Cat’s Claw
1 Celastrol
1 Chlorogenic acid
1 Chlorophyllin
1 Coenzyme Q10
1 Dichloroacetophenone(2,2-)
1 Dichloroacetate
1 Fucoidan
1 Ferulic acid
1 Graviola
1 Hydroxycinnamic-acid
1 hydroxychloroquine
1 Methylene blue
1 Photodynamic Therapy
1 Chemotherapy
1 Myricetin
1 nelfinavir/Viracept
1 Oleuropein
1 SonoDynamic Therapy UltraSound
1 Hyperthermia
1 Plumbagin
1 VitK3,menadione
1 Hyperoside
1 Rosmarinic acid
1 salinomycin
1 Osimertinib
1 Adagrasib
1 Aflavin-3,3′-digallate

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#:239  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

PARP Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Kinase & Signal Transduction ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

Autophagy & Lysosomes ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Cell Death ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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