P21 Cancer Research Results

P21, P21: Click to Expand ⟱

Source:

Type: Proapototic

cyclin-dependent kinase inhibitor p21 (also known as p21 WAF1/Cip1) promotes cell cycle arrest in response to many stimuli.
P21 is a cyclin-dependent kinase inhibitor that plays a crucial role in regulating the cell cycle. It is encoded by the CDKN1A gene and is a key player in the cellular response to stress, including DNA damage.
P21 is often considered a tumor suppressor because its expression is upregulated in response to p53 activation, a well-known tumor suppressor protein. When DNA damage occurs, p53 can activate the transcription of the CDKN1A gene, leading to increased levels of P21, which helps prevent the proliferation of damaged cells.
In many cancers, the p53 pathway is disrupted, leading to decreased levels of P21. p21 is a apoptotic marker protein.
Cell cycle arrest gene p21

Scientific Papers found: Click to Expand⟱

4774-

5-FU,

TQ,

CoQ10,

Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation

in-vitro,

CRC,

AntiCan↑, All treatments resulted in anticancer effects depicted by cell cycle arrest and apoptosis, with TQ demonstrating greater efficacy than CQ10, both with and without 5-FU.
TumCCA↑,
Apoptosis↑,
eff↑,
Bcl-2↓, However, 5-FU/TQ/CQ10 triple therapy exhibited the most potent pro-apoptotic activity in all cell lines, portrayed by the lowest levels of oncogenes (CCND1, CCND3, BCL2, and survivin)
survivin↓,
P21↑, and the highest upregulation of tumour suppressors (p21, p27, BAX, Cytochrome-C, and Cas- pase-3).
p27↑,
BAX↑,
Cyt‑c↑,
Casp3↑,
PI3K↓, The triple therapy also showed the strongest suppression of the PI3K/AKT/mTOR/HIF1α pathway, with a concurrent increase in its endogenous inhibitors (PTEN and AMPKα) in all cell lines used.
Akt↓,
mTOR↓,
Hif1a↓,
PTEN↑,
AMPKα↑,
PDH↑, triple therapy favoured glucose oxidation by upregulating PDH, while decreasing LDHA and PDHK1 enzymes.
LDHA↓,
antiOx↓, most significant decline in antioxidant levels and the highest increases in oxidative stress markers
ROS↑,
AntiCan↑, This study is the first to demonstrate the superior anticancer effects of TQ compared to CQ10, with and without 5-FU, in CRC treatment.

5431-

AG,

Advances in research on the anti-tumor mechanism of Astragalus polysaccharides

Review,

Var,

AntiTum↑, APS has been increasingly used in cancer therapy owing to its anti-tumor ability as it prevents the progression of prostate, liver, cervical, ovarian, and non-small-cell lung cancer by suppressing tumor cell growth and invasion and enhancing apoptosi
TumCG↓,
TumCI↓,
Apoptosis↑, after APS treatment, the apoptosis of HepG2 cells is accelerated (57).
Imm↑, APS enhances the sensitivity of tumors to antineoplastic agents and improves the body’s immunity
Bcl-2↓, Huang et al. proposed that APS induces H22 (a hepatocellular cancer [HCC] cell line) apoptosis by downregulating Bcl-2 and upregulating Bax expression (56).
BAX↑,
Wnt↓, downregulating the Wnt/β-catenin signaling pathway.
β-catenin/ZEB1↓,
TumCG↓, APS effectively inhibited the growth of MDA-MB-231 (a human breast cancer [BC] cell line) graft tumor (58)
miR-133a-3p↑, apoptosis rate of human osteosarcoma MG63 cells increased owing to the upregulation of miR-133a and inactivation of the JNK signaling pathways (71).
JNK↓,
Fas↑, Li and Shen found that APS can induce apoptosis by activating the Fas death receptor pathway.
P53↑, Zhang et al. showed that APS could activate p53 and p21 and inhibit the expression of Notch1 and Notch3 in vitro, ultimately inhibiting cell proliferation and promoting their apoptosis
P21↑,
NOTCH1↓,
NOTCH3↓,
TumCP↓,
TumCCA↑, Liu et al. found that APS induced the cell cycle of bladder cancer UM-UC-3 to stop in the G0/G1 phase, thus inhibiting its proliferation
GPx4↓, APS was found to reduce GPX4 expression, inhibit the activity of the light chain subunit SLC7A11 (xCT), and promote the formation of BECN1-xCT complex by activating AMPK/BECN1 signaling.
xCT↓,
AMPK↑,
Beclin-1↑,
NF-kB↓, APS could control the proliferation of lung cancer cells (A549 and NCI-H358 cells) by inhibiting the NF-κB signaling pathway (97)
EMT↓, APS treatment led to reduced EMT markers (vimentin, AXL) and MIF levels in cells.
Vim↓,
TumMeta↓, APS inhibits Lewis lung cancer growth and metastasis in mice by significantly reducing VEGF and EGFR expression in cancerous tissues
VEGF↓,
EGFR↓,
eff↑, Nano-drug delivery systems can increase efficiency and reduce toxicity
eff↑, Jiao et al. developed selenium nanoparticles modified with macromolecular weight APS and observed positive results in hepatoma treatment
MMP↓, Subsequent investigations revealed that APS can decrease the ΔΨm values and Bcl-2, p-PI3K, P-gp, and p-AKT levels while elevating Bax expression.
P-gp↓,
MMP9↓, downregulation of MMP-9 expression,
ChemoSen↑, Li et al. observed that APS could enhance the sensitivity of SKOV3 ovarian cancer cells to CDDP treatment by activating the mitochondrial apoptosis pathway and JNK1/2 signaling pathway
SIRT1↓, APS significantly suppressed SIRT1 and SREBP1 expression, decreased cholesterol and triglyceride levels in PC3 and DU145, and attenuated cell proliferation.
SREBP1↓,
TumAuto↑, APS can induce autophagy in colorectal cancer cells by inhibiting the PI3K/AKT/mTOR axis and the development of cancer cells.
PI3K↓,
mTOR↓,
Casp3↑, Shen found that APS elevated caspase-9, caspase-3, and Bax protein levels, decreased Bcl-2 protein expression, and inhibited CD133 and CD44 co-positive colon cancer stem cell proliferation time
Casp9↑,
CD133↓,
CD44↓,
CSCs↓,
QoL↑, QOL was significantly improved as indicated by the reduction in pain and improvement in appetite

4430-

AgNPs,

Evaluation of the Genotoxic and Oxidative Damage Potential of Silver Nanoparticles in Human NCM460 and HCT116 Cells

in-vitro,

Colon,

HCT116

20 nm

in-vitro,

Nor,

NCM460

*Bacteria↓, Nano Ag has excellent antibacterial properties and is widely used in various antibacterial materials, such as antibacterial medicine and medical devices, food packaging materials and antibacterial textiles
ROS↑, intracellular reactive oxygen species (ROS) increased
p‑p38↑, Ag NPs can promote the increase in P38 protein phosphorylation levels in two colon cells and promote the expression of P53 and Bax.
BAX↑,
Bcl-2↓, Ag NPs can promote the down-regulation of Bcl-2, leading to an increased Bax/Bcl-2 ratio and activation of P21, further accelerating cell death
BAX↑,
P21↑,
TumCD↑,
toxicity↝, low concentration of nano Ag has no obvious toxic effect on colon cells, while nano Ag with concentrations higher than 15 μg/mL will cause oxidative damage to colon 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.

334-

AgNPs,

Silver-Based Nanoparticles Induce Apoptosis in Human Colon Cancer Cells Mediated Through P53

in-vitro,

Colon,

HCT116

Bax:Bcl2↑, as demonstrated by an increase in 4´,6-diamidino-2-phenylindole-stained apoptotic nuclei, BAX/BCL-XL ratio, cleaved poly(ADP-ribose) polymerase, p53, p21 and caspases 3, 8 and 9, and by a decrease in the levels of AKT and NF-κB.
P53↑, AgNPs are bona fide anticancer agents that act in a p53-dependent manner
P21↑,
Casp3↑,
Casp8↑,
Casp9↑,
Akt↓,
NF-kB↓,
DNAdam↑, AgNPs caused DNA damage and reduced the interaction between p53 and NF-κB
TumCCA↑, The cell population in the G1 phase decreased, and the S-phase population increased after AgNP treatment

324-

AgNPs,

CPT,

Silver Nanoparticles Potentiates Cytotoxicity and Apoptotic Potential of Camptothecin in Human Cervical Cancer Cells

in-vitro,

Cerv,

HeLa

ROS↑,
Casp3↑,
Casp9↑,
Casp6↑,
GSH↓,
SOD↓,
GPx↓,
MMP↓, loss of
P53↑,
P21↑,
Cyt‑c↑,
BID↑,
BAX↑,
Bcl-2↓,
Bcl-xL↓,
Akt↓,
Raf↓,
ERK↓,
MAP2K1/MEK1↓,
JNK↑,
p38↑,

397-

AgNPs,

GEM,

Silver nanoparticles enhance the apoptotic potential of gemcitabine in human ovarian cancer cells: combination therapy for effective cancer treatment

in-vitro,

Ovarian,

A2780S

50 nM GEM, 50 nM AgNPs

6nm

P53↑,
P21↑,
BAX↑,
Bak↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
Bcl-2↓,
ROS↑,
MMP↓,

396-

AgNPs,

Systemic Evaluation of Mechanism of Cytotoxicity in Human Colon Cancer HCT-116 Cells of Silver Nanoparticles Synthesized Using Marine Algae Ulva lactuca Extract

in-vitro,

Colon,

HCT116

P53↑,
BAX↑,
P21↑,
Bcl-2↓,

384-

AgNPs,

Dual functions of silver nanoparticles in F9 teratocarcinoma stem cells, a suitable model for evaluating cytotoxicity- and differentiation-mediated cancer therapy

in-vitro,

Testi,

LDH↓, When the cells were treated with AgNPs and AgNO3, the amount of LDH leaked into the media increased in a dose-dependent manner
ROS↑,
mtDam↑,
DNAdam↑,
P53↑,
P21↑,
BAX↑,
Casp3↑,
Bcl-2↓,
Casp9↑,
Nanog↓,
OCT4↓,

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

2660-

AL,

Allicin: A review of its important pharmacological activities

Review,

AD,

Review,

Var,

Review,

Park,

Review,

Stroke,

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

251-

AL,

Inhibition of allicin in Eca109 and EC9706 cells via G2/M phase arrest and mitochondrial apoptosis pathway

in-vitro,

ESCC,

Eca109

 0-100ug/ml

in-vitro,

ESCC,

EC9706

in-vivo,

NA,

5mg/kg/bw

mice

Apoptosis↑,
P53↑,
P21↑,
CHK1↑,
CycB/CCNB1↓,
BAX↑,
Casp3↑,
Casp9↑,
Cyt‑c↑, allicin treatment resulted in Cyt c release from the mitochondria to the cytosol.

277-

ALA,

α-lipoic acid modulates prostate cancer cell growth and bone cell differentiation

in-vitro,

Pca,

22Rv1

 500 μM

in-vitro,

Pca,

C4-2B

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↑, HIF-1α, is a key regulator in response to cellular stressors, and excessive ROS levels can influence its expression. (HIF-1α) is essential for the physiological response to hypoxia(resulting from elevated intracellular ROS levels)
JNK↑,
Casp3↑,
P21↑,
BAX↑,
Bcl-xL↓,
cFos↓,

259-

ALA,

Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells

in-vitro,

Liver,

HepG2

500 µM for 24, 48 and 72 h

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↓,

5326-

ALC,

L-Carnitine Is an Endogenous HDAC Inhibitor Selectively Inhibiting Cancer Cell Growth In Vivo and In Vitro

vitro+vivo,

Liver,

HepG2

mice

TumCG↓, Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro;
P21↑, (2) LC treatment selectively induces the expression of p21cip1 gene, mRNA and protein in cancer cells
ac‑H3↑, (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells
HDAC↓, (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro;
*ATP↑, LC is able to generate ATP in normal mouse thymocytes, but not in hepatic HepG2 and SMMC-7721 cancer cells.
selectivity↑,
ac‑H4↑, LC dose-dependently increased acetylation of H3 and H4 (

1158-

And,

GEM,

Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer

TumCP↓,
TumCCA↑,
Apoptosis↑,
STAT3↓,
Akt↓,
P21↑,
BAX↑,
cycD1/CCND1↓,
cycE/CCNE↓,
survivin↓,
XIAP↓,
Bcl-2↓,
eff↑, ANDRO combined with gemcitabine significantly induce stronger cell cycle arrest and more obvious apoptosis than each single treatment.

1151-

Api,

Plant flavone apigenin inhibits HDAC and remodels chromatin to induce growth arrest and apoptosis in human prostate cancer cells: In vitro and in vivo study

in-vitro,

Pca,

PC3

20–40μM

in-vitro,

Pca,

22Rv1

in-vivo,

NA,

oral intake of apigenin at doses of 20 and 50μg/mouse/day

mouse

TumCCA↑,
Apoptosis↑,
HDAC↓, HDAC1 and HDAC3
P21↑,
BAX↑,
TumCG↓,
Bcl-2↓,
Bax:Bcl2↑, shifting the bax/bcl2 ratio in favor of apoptosis
HDAC1↓,
HDAC3↓,

1553-

Api,

Role of Apigenin in Cancer Prevention via the Induction of Apoptosis and Autophagy

Review,

NA,

Dose∅, oral administration of apigenin (20 and 50 μg/mice) for 20 weeks reduced tumor volumes
TumVol↓,
Dose∅, 15-week period of oral administration of apigenin (2.5 mg/kg) in hamsters resulted in reduction of tumor volume
COX2↓, topical application of apigenin (5 μM) prior to UVB-exposure attenuated the expression of COX-2 and hypoxia inducible factor (HIF)-1α,
Hif1a↓,
TumCCA↑, apigenin was capable to promote cell cycle arrest and induction of apoptosis through p53-related pathways
P53↑,
P21↑, induction of the cell cycle inhibitor p21/WAF1,
Casp3↑,
DNAdam↑, DNA fragmentation
TumAuto↝, Only a small number of studies have observed the induction of autophagy in response to apigenin and the results are controversial

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↓,

1564-

Api,

Apigenin-induced prostate cancer cell death is initiated by reactive oxygen species and p53 activation

in-vitro,

Pca,

22Rv1

10–80 μM

in-vivo,

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,

 20–60 μM

45.55 μM

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,

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↑,

581-

Api,

Cisplatin,

The natural flavonoid apigenin sensitizes human CD44+ prostate cancer stem cells to cisplatin therapy

in-vitro,

Pca,

CD44+

15uM / 7.5uM for 48

CD44+PCa

Bcl-2↓,
survivin↓,
Casp8↑,
P53↑,
Sharpin↓,
APAF1↑,
p‑Akt↓,
NF-kB↓,
P21↑,
Cyc↓,
CDK2↓,
CDK4/6↓,
Snail↓,
ChemoSen↑, Apigenin significantly increased the inhibitory effects of cisplatin on cell migration via downregulation of Snail expression

177-

Api,

Inhibition of MDA-MB-231 breast cancer cell proliferation and tumor growth by apigenin through induction of G2/M arrest and histone H3 acetylation-mediated p21WAF1/CIP1 expression

in-vitro,

BC,

MDA-MB-231

Cyc↓, Cyclin A
CycB/CCNB1↓,
CDK1↓,
P21↑,
PCNA↝,
HDAC↓, apigenin treatment for 48 h suppressed HDAC activity in MDA-MB-231 cells in a dose-dependent manner
TumCP↓, Apigenin Inhibited MDA-MB-231 Cell Proliferation
TumCCA↑, Apigenin Induced G2/M Arrest in MDA-MB-231 Cells
ac‑H3↑, H3 acetylation increased in time-dependent
TumW↓, apigenin treatment significantly reduced the tumor volume and tumor weight
TumVol↓,

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↓,

207-

Api,

Involvement of nuclear factor-kappa B, Bax and Bcl-2 in induction of cell cycle arrest and apoptosis by apigenin in human prostate carcinoma cells

in-vitro,

Pca,

LNCaP

PSA↓,
cycD1/CCND1↓, cyclinD1 and cyclinD2
cycE/CCNE↓,
CDK2↓,
CDK4/6↓,
P21↑,
AR↓,

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↓,

240-

Api,

The flavonoid apigenin reduces prostate cancer CD44(+) stem cell survival and migration through PI3K/Akt/NF-κB signaling

in-vitro,

Pca,

PC3

 25 uM

in-vitro,

Pca,

CD44+

P21↑,
p27↑,
Casp3↑,
Casp8↑,
Slug↓,
Snail↓,
NF-kB↓,
PI3K↓,
Akt↓,

3391-

ART/DHA,

Antitumor Activity of Artemisinin and Its Derivatives: From a Well-Known Antimalarial Agent to a Potential Anticancer Drug

Review,

Var,

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

3160-

Ash,

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

Review,

Var,

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↓,

3162-

Ash,

Molecular insights into cancer therapeutic effects of the dietary medicinal phytochemical withaferin A

Review,

Var,

lipid-P↓, Oral cancer 20 mg/Kg ↓Lipid peroxidation : ↑SOD, glutathione peroxidase, p53, Bcl-2
SOD↑,
GPx↑,
P53↑,
Bcl-2↑,
E6↓, Cervival cancer 8mg/Kg ↓E6, E7: ↑p53, pRb, Cyclin B1, P34 Cdc2, p21, PCNA
E7↓,
pRB↑,
CycB/CCNB1↑,
CDC2↑,
P21↑,
PCNA↓,
ALDH1A1↓, Mammary cancer 0-1 mg/mouse (5-10) ↓Mammosphere number, ALDH1 activity. Vimentin, glycolysis
Vim↓,
Glycolysis↓,
cMyc↓, Mesotheliome cancer 5 mg/Kg ↓Proteasomal chymotrypsin, C-Myc : ↑ Bax, CARP-1
BAX↑,
NF-kB↓,
Casp3↑, caspase-3 activation
CHOP↑, WA is found to increase activation of Elk1 and CHOP (CCAAT-enhancer-binding protein homologous protein) by RSK, as well as up-regulation of DR5 by selectively suppressing pathway ERK
DR5↑,
ERK↓,
Wnt↓, WA inhibits Wnt/Î²-catenin pathway via suppression of AKT signalling, which inhibits cancer cell motility and sensitises for cell death
β-catenin/ZEB1↓,
Akt↓,
HSP90↓, WA-dependent inhibition of heat shock protein (HSP) chaperone functions. WA inhibits the activity of HSP90-mediated function

4820-

ASTX,

Astaxanthin suppresses the malignant behaviors of nasopharyngeal carcinoma cells by blocking PI3K/AKT and NF-κB pathways via miR-29a-3p

in-vitro,

NPC,

0, 1, 10, 20 mg/mL

TumCP↓, C666-1 cell proliferation, invasion, and migration were significantly suppressed by astaxanthin while cell apoptosis and cell cycle arrest at G1 phase were effectively enhanced in the context of 10 mg/mL astaxanthin.
TumCI↓,
Apoptosis↑,
TumCCA↑,
cycD1/CCND1↓, inhibitory effect of astaxanthin on Cyclin D1 and Bcl-2 protein levels as well as the promoting impact of astaxanthin on p21 and Bax were also amplified in combination with LY294002 or PTL treatment.
Bcl-2↓,
P21↑,
BAX↑,
PI3K↓, Astaxanthin significantly suppresses NPC cell proliferation, cell cycle arrest, migration, invasion while promoting cell apoptosis by inactivating PI3K/AKT and NF-κB pathways.
Akt↓,
NF-kB↓,
miR-29b↑, Astaxanthin upregulates miR-29a-3p expression to inactivate the PI3K/AKT and NF-κB pathways

4819-

ASTX,

Astaxanthin Induces Apoptosis in MCF-7 Cells through a p53-Dependent Pathway

in-vitro,

BC,

MCF-7

5, 10, 25, 50, 75, 100, 125, and 150 μg/mL)

IC50 = 89.742 μg/mL

antiOx↑, It is well known that AXT plays a role as a drug with antioxidant and antitumor properties
AntiTum↑,
TumCD↑, The treatment induced the decrease in cell number in a dose-dependent manner
P53↑, it was observed that the expression of p53 and p21 increased proportionally to the concentration of the AXT treatment.
P21↑,
Apoptosis↑, These findings suggest that the apoptosis of MCF-7 cells induced by AXT operates through a p53-dependent pathway, implying that AXT could potentially have a beneficial role in future breast cancer treatments.
Dose↝, Treatment with 50 μg/mL of AXT led to a viability of the tumor cell of approximately 30% after 48 h.
Casp3↑, The results indicated that caspase-3 activity increased following AXT treatment, reaching a maximum at 48 h post treatment

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

1532-

Ba,

Baicalein as Promising Anticancer Agent: A Comprehensive Analysis on Molecular Mechanisms and Therapeutic Perspectives

Review,

NA,

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

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

2290-

Ba,

Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer

Review,

GI,

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

5551-

BBM,

Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis

vitro+vivo,

Bladder,

tumCV↓, our results showed that berbamine inhibited cell viability, colony formation, and proliferation.
TumCP↓,
TumCCA↑, Additionally, berbamine induced cell cycle arrest at S phase by a synergistic mechanism involving stimulation of P21 and P27 protein expression
P21↑,
p27↑,
cycD1/CCND1↓, as well as downregulation of CyclinD, CyclinA2, and CDK2 protein expression.
cycA1/CCNA1↓,
CDK2↓,
EMT↓, In addition to suppressing epithelial-mesenchymal transition (EMT), berbamine rearranged the cytoskeleton to inhibit cell metastasis.
TumMeta↓,
p65↓, Mechanistically, the expression of P65, P-P65, and P-IκBα was decreased upon berbamine treatment
p‑p65↓,
IKKα↓,
NF-kB↑, berbamine attenuated the malignant biological activities of BCa cells by inhibiting the NF-κB pathway.
ROS↑, More importantly, berbamine increased the intracellular reactive oxygen species (ROS) level through the downregulation of antioxidative genes such as Nrf2, HO-1, SOD2, and GPX-1.
NRF2↓,
HO-1↓,
SOD2↓,
GPx1↓,
Bax:Bcl2↑, increase in the ratio of Bax/Bcl-2.
TumVol↓, berbamine successfully inhibited tumor growth and blocked the NF-κB pathway in our xenograft model

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.

1393-

BBR,

EPI,

Berberine promotes antiproliferative effects of epirubicin in T24 bladder cancer cells by enhancing apoptosis and cell cycle arrest

in-vitro,

Bladder,

T24/HTB-9

ChemoSen↑, Ber enhanced the inhibitory effect of EPI on the viability of T24 cells
TumCCA↑, cycle arrest at G0/G1
Apoptosis↑,
cl‑Casp3↑,
cl‑Casp9↑,
BAX↑,
P53↑,
P21↑,
Bcl-2↓,
ROS↑, Ber significantly increased ROS production

1299-

BBR,

Effects of Berberine and Its Derivatives on Cancer: A Systems Pharmacology Review

Review,

NA,

TumCCA↑, G1 phase, G0/G1 phase, or G2/M phase
TP53↑,
COX2↓,
Bax:Bcl2↑,
ROS↑,
VEGFR2↓,
Akt↓,
ERK↓,
MMP2↓, Berberine also decreased MMP-2, MMP-9, E-cadherin, EGF, bFGF, and fibronectin in the breast cancer cells.
MMP9↓,
IL8↑,
P21↑,
p27↑,
E-cadherin↓,
Fibronectin↓,
cMyc↓, The results indicated that these derivatives could selectively induce and stabilize the formation of the c-myc in the parallel molecular G-quadruplex. Accordingly, transcription of c-myc was down-regulated in the cancer cell line

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↓,

4658-

BBR,

Berberine Suppresses Stemness and Tumorigenicity of Colorectal Cancer Stem-Like Cells by Inhibiting m6A Methylation

in-vitro,

CRC,

HCT116

in-vitro,

CRC,

HT29

CSCs↓, Our observation that Berberine effectively decreased m6A methylation by decreasing β-catenin and subsequently increased FTO suggests a role of Berberine in modulating stemness and malignant behaviors in colorectal CSCs.
TumCP↓, Berberine treatment decreased cell proliferation by decreasing cyclin D1 and increasing p27 and p21 and subsequently induced cell cycle arrest at the G1/G0 phase.
cycD1/CCND1↓,
p27↑,
P21↑,
TumCCA↑,
Apoptosis↑, Berberine treatment also decreased colony formation and induced apoptosis.
ChemoSen↑, Berberine treatment also increased chemosensitivity in CSCs and promoted chemotherapy agent-induced apoptosis.
β-catenin/ZEB1↓, Berberine treatment increased FTO by decreasing β-catenin, which is a negative regulator of FTO.
FTO↑,
CD44↓, Consistently, CD44 and CD133 were decreased by Berberine treatment
CD133↓,
ChemoSen↑, Berberine Enhanced Chemosensitivity via Regulating FTO

5178-

BBR,

Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells

in-vitro,

Pca,

DU145

in-vitro,

Pca,

PC3

TumCP↑, Here, we report that in vitro treatment of androgen-insensitive (DU145 and PC-3) and androgen-sensitive (LNCaP) prostate cancer cells with berberine inhibited cell proliferation and induced cell death in a dose-dependent (10–100 μmol/L) and time-depe
TumCCA↑, associated with G1-phase arrest, which in DU145 cells was associated with inhibition of expression of cyclins D1, D2, and E and cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 proteins,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
P21↑, increased expression of the Cdk inhibitory proteins (Cip1/p21 and Kip1/p27), and enhanced binding of Cdk inhibitors to Cdk.
p27↑,
Apoptosis↑, Berberine also significantly (P < 0.05–0.001) enhanced apoptosis of DU145 and LNCaP cells with induction of a higher ratio of Bax/Bcl-2 proteins
Bax:Bcl2↑,
MMP↓, disruption of mitochondrial membrane potential, and activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase.
Casp9↑,
Casp3↑,
PARP↑,
DNAdam↑, analysis of DNA fragmentation
selectivity↑, Berberine Inhibits Proliferation and Viability and Induces the Death of Prostate Cancer Cells but not of Normal Prostate Epithelial Cells
Cyt‑c↑, Berberine Induces the Disruption of Mitochondrial Membrane Potential and Increases the Release of Cytochrome c

5633-

BCA,

Mechanisms Behind the Pharmacological Application of Biochanin-A: A review

Review,

Var,

Review,

AD,

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

5634-

BCA,

Molecular Mechanisms of Biochanin A in AML Cells: Apoptosis Induction and Pathway-Specific Regulation in U937 and THP-1

in-vitro,

AML,

U937

in-vitro,

AML,

THP1

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

5636-

BCA,

Biochanin A Induces S Phase Arrest and Apoptosis in Lung Cancer Cells

vitro+vivo,

Lung,

A549

tumCV↓, Biochanin A decreased cell viability in a time-dependent and dose-dependent manner and suppressed colony formation in A549 and 95D cells.
TumCCA↑, Biochanin A induced S phase arrest and apoptosis and decreased mitochondrial membrane potential (ΔΨm) in A549 and 95D cells in a dose-dependent manner.
Apoptosis↑,
MMP↓,
TumCG↓, Our results of subcutaneous xenograft models showed that the growth of Biochanin A group was significantly inhibited compared with that of control groups.
P21↑, Finally, P21, Caspase-3, and Bcl-2 were activated in Biochanin A-treated cells and Biochanin A-treated xenografts
Casp3↑,
Bcl-2↑,

5639-

BCA,

Biochanin A Induces Apoptosis in MCF-7 Breast Cancer Cells through Mitochondrial Pathway and Pi3K/AKT Inhibition

in-vitro,

BC,

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

2718-

BetA,

The anti-cancer effect of betulinic acid in u937 human leukemia cells is mediated through ROS-dependent cell cycle arrest and apoptosis

in-vitro,

AML,

U937

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

Showing Research Papers: 1 to 50 of 219
Page 1 of 5 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 219

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 4, GPx↑, 1, GSH↑, 1, GSTs↑, 1, Keap1↓, 1, lipid-P↓, 2, MDA↓, 1, MPO↓, 1, NRF2↑, 3, Prx↑, 1, ROS↓, 4, SOD↑, 2, SOD2↑, 1, TBARS↓, 1,

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1, H2S↑, 1, LDH↓, 2,

Cell Death ⓘ

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

Transcription & Epigenetics ⓘ

other↑, 1,

Proliferation, Differentiation & Cell State ⓘ

PI3K↓, 1,

Migration ⓘ

PKCδ↓, 1,

Angiogenesis & Vasculature ⓘ

NO↓, 1,

Barriers & Transport ⓘ

BBB↑, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 1, IL6↓, 1, Inflam↓, 5, NF-kB↓, 2, PGE2↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 1,

Protein Aggregation ⓘ

BACE↓, 1,

Hormonal & Nuclear Receptors ⓘ

CYP19↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, eff↑, 1, Half-Life↝, 1, Half-Life∅, 1,

Clinical Biomarkers ⓘ

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

Functional Outcomes ⓘ

AntiDiabetic↑, 1, cardioP↑, 2, chemoP↑, 1, cognitive↑, 1, hepatoP↑, 3, memory↑, 2, neuroP↑, 5, Obesity↓, 1, toxicity↓, 3,

Infection & Microbiome ⓘ

Bacteria↓, 2,
Total Targets: 58

Scientific Paper Hit Count for: P21, P21

19 Thymoquinone
12 Apigenin (mainly Parsley)
12 Curcumin
11 Sulforaphane (mainly Broccoli)
8 Silver-NanoParticles
8 EGCG (Epigallocatechin Gallate)
7 Fisetin
6 Lycopene
6 Quercetin
6 Resveratrol
5 Berberine
5 Magnolol
5 Propolis -bee glue
5 Phenethyl isothiocyanate
5 Piperlongumine
5 Urolithin
4 Allicin (mainly Garlic)
4 Biochanin A
4 Boswellia (frankincense)
4 Ellagic acid
4 Phenylbutyrate
3 Gemcitabine (Gemzar)
3 Cisplatin
3 Baicalein
3 Capsaicin
3 Emodin
3 Honokiol
3 Luteolin
3 salinomycin
3 Silymarin (Milk Thistle) silibinin
3 Shikonin
2 Alpha-Lipoic-Acid
2 Ashwagandha(Withaferin A)
2 Astaxanthin
2 Berbamine
2 Betulinic acid
2 Caffeic acid
2 Carnosic acid
2 Carvacrol
2 Thymol-Thymus vulgaris
2 Chlorogenic acid
2 diet Methionine-Restricted Diet
2 Gallic acid
2 Garcinol
2 HydroxyTyrosol
2 Magnetic Fields
2 Naringin
2 Oleuropein
2 Plumbagin
2 Rosmarinic acid
2 Ursolic acid
1 5-fluorouracil
1 Coenzyme Q10
1 Astragalus
1 Camptothecin
1 Acetyl-l-carnitine
1 Andrographis
1 Artemisinin
1 Atorvastatin
1 epirubicin
1 Chrysin
1 Butyrate
1 Ferulic acid
1 Fenbendazole
1 Gambogic Acid
1 Genistein (soy isoflavone)
1 Hydroxycinnamic-acid
1 Inositol
1 Juglone
1 Melatonin
1 acetazolamide
1 Aflavin-3,3′-digallate
1 doxorubicin
1 Oxaliplatin
1 Vitamin C (Ascorbic Acid)
1 Magnesium

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

P21 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 ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Hormonal & Nuclear Receptors ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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