Bax:Bcl2 Cancer Research Results

Bax:Bcl2, Bax:Bcl2 ratio: Click to Expand ⟱

Source:

Type:

Bax and Bcl-2 are the major members of Bcl-2 family that play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction.
Bax/Bcl-2 ratio is typically significantly lower in tumors.

Scientific Papers found: Click to Expand⟱

2327-

2DG,

2-Deoxy-d-Glucose and Its Analogs: From Diagnostic to Therapeutic Agents

Review,

Var,

Glycolysis↓, 2-DG inhibits glycolysis due to formation and intracellular accumulation of 2-deoxy-d-glucose-6-phosphate (2-DG6P), inhibiting the function of hexokinase and glucose-6-phosphate isomerase, and inducing cell death
HK2↓,
mt-ROS↑, 2-DG-mediated glucose deprivation stimulates reactive oxygen species (ROS) production in mitochondria, also leading to AMPK activation and autophagy stimulation.
AMPK↑,
PPP↓, 2-DG has been shown to block the pentose phosphate shunt
NADPH↓, Decreased levels of NADPH correlate with reduced glutathione levels, one of the major cellular antioxidants.
GSH↓,
Bax:Bcl2↑, Valera et al. also observed that in bladder cancer cells, 2-DG treatment modulates the Bcl-2/Bax protein ratio, driving apoptosis induction
Apoptosis↑,
RadioS↑, 2-DG radiosensitization results from its effect on thiol metabolism
eff↓, (NAC) treatment, downregulated glutamate cysteine ligase activity, or overexpression of ROS scavenging enzymes
Half-Life↓, its plasma half-life was only 48 min [117]) make 2-DG a rather poor drug candidate
other↝, Adverse effects of 2-DG administration in humans include fatigue, sweating, dizziness, and nausea, mimicking the symptoms of hypoglycemia
eff↓, Moreover, 2-DG has to be used at relatively high concentrations (≥5 mmol/L) in order to compete with blood glucose

1295-

AG,

Cisplatin,

Chemosensitizing Effect of Astragalus Polysaccharides on Nasopharyngeal Carcinoma Cells by Inducing Apoptosis and Modulating Expression of Bax/Bcl-2 Ratio and Caspases

in-vivo,

Laryn,

mice

AntiTum↑,
Apoptosis↑,
Bcl-2↓,
BAX↑,
Casp3↑,
Casp9↑,
Bax:Bcl2↑, ratio of Bax to Bcl-2 was significantly enhanced by the APS to cisplatin

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

377-

AgNPs,

Anticancer Action of Silver Nanoparticles in SKBR3 Breast Cancer Cells through Promotion of Oxidative Stress and Apoptosis

in-vitro,

BC,

SkBr3

ROS↑,
Apoptosis↑,
Bax:Bcl2↑,
VEGF↑, VEGF-A
Akt↓,
PI3K↓,
TAC↓,
TOS↑,
OSI↑,
MDA↑,
Casp3↑,
Casp7↑,

254-

AL,

Allicin and Cancer Hallmarks

Review,

Var,

NRF2⇅, 40 nM
BAX↑,
Bcl-2↓,
Fas↑,
MMP↓,
Bax:Bcl2↑,
Cyt‑c↑,
Casp3↑,
Casp12↑,
GSH↓, Allicin can easily penetrate the cell membrane and react with the cellular thiol to transiently deplete the intracellular GSH level, inducing the inhibition of cell cycle progression and growth arrest [98].
TumCCA↑,
ROS↑, An in vitro study indicated that allicin encourages oxidative stress and autophagy in Saos-2 and U2OS (osteosarcoma cells) by modulating the MALATI-miR-376a-Wnt and β-catenin pathway [99].
antiOx↓, As an antioxidant phytochemical, it scavenges reactive oxygen species (ROS) and protects cells from oxidative DNA damage [34].

261-

ALA,

The natural antioxidant alpha-lipoic acid induces p27(Kip1)-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells

in-vitro,

BC,

MCF-7

 0-2.5mM

ROS↓, We observed that alpha-lipoic acid is able to scavenge reactive oxygen species in MCF-7 cells(52%)
Akt↓,
p27↑,
Bax:Bcl2↑,

1078-

And,

Andrographolide inhibits breast cancer through suppressing COX-2 expression and angiogenesis via inactivation of p300 signaling and VEGF pathway

in-vitro,

BC,

MDA-MB-231

5, 10, 25 and 50 μM

20uM

in-vitro,

Nor,

HUVECs

50uM

in-vivo,

BC,

MCF-7

35uM

xenografts nude mice

in-vitro,

BC,

T47D

32uM

in-vitro,

BC,

BT549

23uM

in-vitro,

BC,

MDA-MB-361

31uM

TumCP↓,
COX2↓, suppress COX-2 expression at both protein and mRNA levels.
*angioG↓,
Cyt‑c↑,
CREB2↓, inhibited the binding of the transactivators CREB2, C-Fos and NF-κB
cFos↓,
NF-kB↓,
HATs↓,
cl‑Casp3↑,
cl‑Casp9↑,
Bax:Bcl2↑,
Apoptosis↑,
*toxicity↓, IC50: 50uM for normal vs 20-35uM for cancer cells

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↓,

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↓,

1547-

Api,

Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading

Review,

NA,

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

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.

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↑,

416-

Api,

In Vitro and In Vivo Anti-tumoral Effects of the Flavonoid Apigenin in Malignant Mesothelioma

vitro+vivo,

NA,

20 mg/kg (C57BL/6 mice, oral gavage)

Malignant mesothelioma (MM)

Bax:Bcl2↑,
P53↑,
ROS↑,
Casp9↑,
Casp8↑,
cl‑PARP1↑, cleavage
p‑ERK⇅, Here, we demonstrated that API treatment was able to increase ERK1/2 phosphorylation in MM-B1, H-Meso-1, and #40a cells while induced a decrease of ERK1/2 activation in MM-F1 cells.
p‑JNK↓,
p‑p38↑,
p‑Akt↓,
cJun↓,
NF-kB↓,
EGFR↓,
TumCCA↑, increase of the percentage of cells in subG1 phase

1367-

Ash,

An anti-cancerous protein fraction from Withania somnifera induces ROS-dependent mitochondria-mediated apoptosis in human MDA-MB-231 breast cancer cells

in-vitro,

BC,

MDA-MB-231

92 μg/mL

Apoptosis↑,
ROS↑, extensive reactive oxygen species generation
Bax:Bcl2↑,
MMP↓,
Casp3↑,
TumCCA↑, G2/M-phase cell cycle arrest

5387-

AsP,

PacT,

Ascorbyl palmitate-incorporated paclitaxel-loaded composite nanoparticles for synergistic anti-tumoral therapy

in-vivo,

Melanoma,

B16-F10

Dose↝, we developed a dual drug delivery system to encapsulate ascorbyl palmitate (AP) and paclitaxel (PTX) for synergistic cancer therapy. 223 nm
TumCG↓, In vivo, AP/PTX-SLNs were revealed to be much more effective in suppressing tumor growth in B16F10-bearing mice and in eliminating cancer cells in the lungs
TumCP↓, AP has been found to inhibit the cell proliferation and DNA synthesis of various cancer cells, including breast, colon, glioblastoma, skin, and brain cancer cells (Naidu, 2003a).
BioAv↓, AP is limited due to its water insolubility, rapid degradation (accelerated by metal ions and/or light), and low bioavailability.
BioAv↑, Therefore, new technologies including nanoparticles that can enhance its delivery efficacy and reduce the dose of administration for Vc while not reducing its anti-cancer efficacy are highly desired.
other↑, These results conformed to the conclusion that only high doses of ascorbic acid have the ability to induce cancer cell death.
Apoptosis↑, Conclusively, the AP/PTX-SLNs exhibited a greater efficacy in inducing cell apoptosis by reducing the Bcl-2/Bax ratio accompanied by promoting tubulin polymerization
Bax:Bcl2↑,
EPR↑, such nanocarriers to permeate into tumor sites because of the enhanced permeation and retention (EPR) effect.
toxicity↝, AP/PTX synergistic combination-based SLN therapy did not induce toxicity and represents a promising strategy for paclitaxel/the vitamin C derivative in promoting anti-cancer effects.

147-

ATG,

EGCG,

CUR,

Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells

in-vitro,

Pca,

LNCaP

  5–10μM Cur, 1μM Arc and 40μM EGCG

in-vitro,

Pca,

MCF-7

  5–10μM Cur, 1μM Arc and 40μM EGCG

Bax:Bcl2↑, combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3
NF-kB↓, arctigenin demonstrated the strongest ability to inhibit the activation of both PI3K/Akt and NFκB pathways in both LNCaP and MCF-7 cells.
PI3K/Akt↓,
STAT3↓,
chemoPv↑, combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.
TumCP↓, combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.
TumCCA↑, EGCG significantly increased the effect of curcumin on cell cycle arrest at G0/G1 phase in MCF-7 cells, and the effect was further enhanced by the addition of arctigenin
TumCMig↓, EGCG and arctigenin alone or in combination with curcumin significantly decreased the number of migrated MCF-7 cells compared to control

1053-

Ba,

docx,

Baicalin, a Potent Inhibitor of NF-κB Signaling Pathway, Enhances Chemosensitivity of Breast Cancer Cells to Docetaxel and Inhibits Tumor Growth and Metastasis Both In Vitro and In Vivo

in-vivo,

BC,

4T1

mouse

TumCP↓,
Apoptosis↑,
ROS↑, cellular induction of reactive oxygen species
Bax:Bcl2↑,
NF-kB↓,
ChemoSen↑, BA sensitized BC cells to docetaxel (DXL) by suppressing the expression of survivin/Bcl-2
survivin↓,

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↓,

2477-

Ba,

Baicalein induces apoptosis via a mitochondrial-dependent caspase activation pathway in T24 bladder cancer cells

in-vitro,

CRC,

T24/HTB-9

TumCG↓, Baicalein inhibited growth and caused G1/S arrest of the cell cycle in the T24 cells.
TumCCA↑,
MMP↓, baicalein induced apoptosis via loss of mitochondrial transmembrane potential (ΔΨm), release of cytochrome c and activation of caspase-9 and caspase-3.
Cyt‑c↑,
Casp9↑,
Casp3↑,
p‑Akt↓, Baicalein inhibited Akt phosphorylation, downregulated Bcl-2 expression and upregulated Bax expression, which in turn increased the ratio of Bax/Bcl-2.
Bcl-2↓,
BAX↑,
Bax:Bcl2↑,
12LOX↓, Baicalein is a well-known inhibitor of 12-lipoxygenase (12-LOX)

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

5547-

BBM,

Berbamine exerts anticancer effects on human colon cancer cells via induction of autophagy and apoptosis, inhibition of cell migration and MEK/ERK signalling pathway

in-vitro,

CRC,

HT29

tumCV↓, Berbamine caused a remarkable decrease in the HT-29 cell viability with an IC50 of 14 µM, while the high IC50 of Berbamine against the normal CDD-18Co cells indicated low toxicity of this molecule against the normal cells.
selectivity↑,
Casp3↑, Berbamine also caused activation of caspase-3 and 9 and increased the Bax/Bcl-2 ratio.
Casp9↑,
Bax:Bcl2↑,
ATG5↑, increase in protein levels of LC3B-I, ATG-5, ATG-12 and Beclin-1.
Beclin-1↑,
TumCP↓, Berbamine decreased the migration potential of the HT-29 and also blocked the MEK/ERK signalling pathway in colon cancer cells.
MEK↓,
ERK↓,

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

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

1377-

BBR,

Berberine inhibits autophagy and promotes apoptosis of fibroblast-like synovial cells from rheumatoid arthritis patients through the ROS/mTOR signaling pathway

in-vitro,

Arthritis,

10, 20, 30, 40, 50, 60, 70, and 80 μmol/L berberine

Apoptosis↑, 30 μmol/L
MMP↓,
Bax:Bcl2↑,
LC3‑Ⅱ/LC3‑Ⅰ↓, Berberine treatment obviously decreased the ratios of Bcl-2/Bax (P < 0.05) and LC3B-II/I (P < 0.01)
p62↑,
*ROS↓,

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↑,

2685-

BBR,

Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells

in-vitro,

neuroblastoma,

CSCs↓, Berberine attenuated cancer stemness markers CD133, β-catenin, n-myc, sox2, notch2 and nestin.
CD133↓,
β-catenin/ZEB1↓,
n-MYC↓,
SOX2↓,
NOTCH2↓,
Nestin↓,
TumCCA↑, Berberine potentiated G0/G1 cell cycle arrest by inhibiting proliferation, cyclin dependent kinases and cyclins resulting in apoptosis through increased bax/bcl-2 ratio.
TumCP↓,
CDK1↓,
Cyc↓,
Apoptosis↑,
Bax:Bcl2↑,
NCAM↓, The induction of NCAM and reduction in its polysialylation indicates anti-migratory potential which is supported by down regulation of MMP-2/9.
MMP2↓,
MMP9↓,
*Smad1↑, It increased epithelial marker laminin and smad and increased Hsp70 levels also suggest its protective role.
*HSP70/HSPA5↑,
*LAMs↑,

2686-

BBR,

Effects of resveratrol, curcumin, berberine and other nutraceuticals on aging, cancer development, cancer stem cells and microRNAs

Review,

Nor,

Inflam↓, BBR has documented to have anti-diabetic, anti-inflammatory and anti-microbial (both anti-bacterial and anti-fungal) properties.
IL6↓, BBRs can inhibit IL-6, TNF-alpha, monocyte chemo-attractant protein 1 (MCP1) and COX-2 production and expression.
MCP1↓,
COX2↓,
PGE2↓, BBRs can also effect prostaglandin E2 (PGE2)
MMP2↓, and decrease the expression of key genes involved in metastasis including: MMP2 and MMP9.
MMP9↓,
DNAdam↑, BBR induces double strand DNA breaks and has similar effects as ionizing radiation
eff↝, In some cell types, this response has been reported to be TP53-dependent
Telomerase↓, This positively-charged nitrogen may result in the strong complex formations between BBR and nucleic acids and induce telomerase inhibition and topoisomerase poisoning
Bcl-2↓, BBR have been shown to suppress BCL-2 and expression of other genes by interacting with the TATA-binding protein and the TATA-box in certain gene promoter regions
AMPK↑, BBR has been shown in some studies to localize to the mitochondria and inhibit the electron transport chain and activate AMPK.
ROS↑, targeting the activity of mTOR/S6 and the generation of ROS
MMP↓, BBR has been shown to decrease mitochondrial membrane potential and intracellular ATP levels.
ATP↓,
p‑mTORC1↓, BBR induces AMPK activation and inhibits mTORC1 phosphorylation by suppressing phosphorylation of S6K at Thr 389 and S6 at Ser 240/244
p‑S6K↓,
ERK↓, BBR also suppresses ERK activation in MIA-PaCa-2 cells in response to fetal bovine serum, insulin or neurotensin stimulation
PI3K↓, Activation of AMPK is associated with inhibition of the PI3K/PTEN/Akt/mTORC1 and Raf/MEK/ERK pathways which are associated with cellular proliferation.
PTEN↑, RES was determined to upregulate phosphatase and tensin homolog (PTEN) expression and decrease the expression of activated Akt. In HCT116 cells, PTEN inhibits Akt signaling and proliferation.
Akt↓,
Raf↓,
MEK↓,
Dose↓, The effects of low doses of BBR (300 nM) on MIA-PaCa-2 cells were determined to be dependent on AMPK as knockdown of the alpha1 and alpha2 catalytic subunits of AMPK prevented the inhibitory effects of BBR on mTORC1 and ERK activities and DNA synthes
Dose↑, In contrast, higher doses of BBR inhibited mTORC1 and ERK activities and DNA synthesis by AMPK-independent mechanisms [223,224].
selectivity↑, BBR has been shown to have minimal effects on “normal cells” but has anti-proliferative effects on cancer cells (e.g., breast, liver, CRC cells) [225–227].
TumCCA↑, BBR induces G1 phase arrest in pancreatic cancer cells, while other drugs such as gemcitabine induce S-phase arrest
eff↑, BBR was determined to enhance the effects of epirubicin (EPI) on T24 bladder cancer cells
EGFR↓, In some glioblastoma cells, BBR has been shown to inhibit EGFR signaling by suppression of the Raf/MEK/ERK pathway but not AKT signaling
Glycolysis↓, accompanied by impaired glycolytic capacity.
Dose?, The IC50 for BBR was determined to be 134 micrograms/ml.
p27↑, Increased p27Kip1 and decreased CDK2, CDK4, Cyclin D and Cyclin E were observed.
CDK2↓,
CDK4↓,
cycD1/CCND1↓,
cycE/CCNE↓,
Bax:Bcl2↑, Increased BAX/BCL2 ratio was observed.
Casp3↑, The mitochondrial membrane potential was disrupted and activated caspase 3 and caspases 9 were observed
Casp9↑,
VEGFR2↓, BBR treatment decreased VEGFR, Akt and ERK1,2 activation and the expression of MMP2 and MMP9 [235].
ChemoSen↑, BBR has been shown to increase the anti-tumor effects of tamoxifen (TAM) in both drug-sensitive MCF-7 and drug-resistant MCF-7/TAM cells.
eff↑, The combination of BBR and CUR has been shown to be effective in suppressing the growth of certain breast cancer cell lines.
eff↑, BBR has been shown to synergize with the HSP-90 inhibitor NVP-AUY922 in inducing death of human CRC.
PGE2↓, BBR inhibits COX2 and PEG2 in CRC.
JAK2↓, BBR prevented the invasion and metastasis of CRC cells via inhibiting the COX2/PGE2 and JAK2/STAT3 signaling pathways.
STAT3↓,
CXCR4↓, BBR has been observed to inhibit the expression of the chemokine receptors (CXCR4 and CCR7) at the mRNA level in esophageal cancer cells.
CCR7↓,
uPA↓, BBR has also been shown to induce plasminogen activator inhibitor-1 (PAI-1) and suppress uPA in HCC cells which suppressed their invasiveness and motility.
CSCs↓, BBR has been shown to inhibit stemness, EMT and induce neuronal differentiation in neuroblastoma cells. BBR inhibited the expression of many genes associated with neuronal differentiation
EMT↓,
Diff↓,
CD133↓, BBR also suppressed the expression of many genes associated with cancer stemness such as beta-catenin, CD133, NESTIN, N-MYC, NOTCH and SOX2
Nestin↓,
n-MYC↓,
NOTCH↓,
SOX2↓,
Hif1a↓, BBR inhibited HIF-1alpha and VEGF expression in prostate cancer cells and increased their radio-sensitivity in in vitro as well as in animal studies [290].
VEGF↓,
RadioS↑,

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

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;

1450-

Bos,

Cisplatin,

3-Acetyl-11-keto-β-boswellic acid (AKBA) induced antiproliferative effect by suppressing Notch signaling pathway and synergistic interaction with cisplatin against prostate cancer cells

in-vitro,

Pca,

DU145

16.50 µM at 48 h

ROS↑, increased reactive oxygen species (ROS) generation
MMP↓,
Casp↑,
Apoptosis↑,
Bax:Bcl2↑,
TumCCA?, induce G0/G1 arrest
cycD1/CCND1↓,
CDK4↓,
P21↑,
p27↑,
NOTCH↓, AKBA demonstrated significant downregulation of Notch signaling mediators
ChemoSen↑, AKBA has the potential to synergistically enhance the cytotoxic efficacy of cisplatin

1651-

CA,

PBG,

Caffeic acid and its derivatives as potential modulators of oncogenic molecular pathways: New hope in the fight against cancer

Review,

Var,

Apoptosis↑,
TumCCA↓, CAPE (1-80 uM) can stimulate apoptosis and cell cycle arrest (G1 phase
TumCMig↓,
TumMeta↓,
ChemoSen↑,
eff↑, Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy.
eff↑, improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid
eff↓, Currently, solvent extraction is utilized by methanol and ethyl acetate combination at high temperatures. However, a low amount of CA is yielded via this pathway
eff↝, Decyl CA (DCA) is a novel derivative of CA but its role in affecting colorectal cancer has not been completely understood.
Dose∅, The CAPE administration (0-60 uM) induces both autophagy and apoptosis in C6 glioma cells.
AMPK↑, CAPE induces autophagy via AMPK upregulation.
p62↓, CAPE can induce autophagy via p62 down-regulation and LC3-II upregulation
LC3II↑,
Ca+2↑, CA (0-1000 uM) enhances Ca2+ accumulation in cells in a concentration-dependent manner
Bax:Bcl2↑, CA can promote Bax/Bcl-2 ratio i
CDK4↑, The administration of CAPE (1–80 μM) can stimulate apoptosis and cell cycle arrest (G1 phase) via upregulation of Bax, CDK4, CDK6 and Rb
CDK6↑,
RB1↑,
EMT↓, CAPE has demonstrated high potential in inhibiting EMT in nasopharyngeal caner via enhancing E-cadherin levels, and reducing vimentin and β-catenin levels.
E-cadherin↑,
Vim↓,
β-catenin/ZEB1↓,
NF-kB↓,
angioG↑, CAPE (0.01-1ug/ml) inhibited angiogenesis via VEGF down-regulation
VEGF↓,
TSP-1↑, and furthermore, CAPE is capable of increasing TSP-1 levels
MMP9↓, CAPE was found to reduce MMP-9 expression
MMP2↓, CAPE can also down-regulate MMP-2
ChemoSen↑, role of CA and its derivatives in enhancing therapy sensitivity of cancer cells.
eff↑, CA administration (100 uM) alone or its combination with metformin (10 mM) can induce AMPK signaling
ROS↑, CA can promote ROS levels to induce cell death in human squamous cell carcinoma
CSCs↓, CA can reduce self-renewal capacity of CSCs and their migratory ability in vitro and in vivo.
Fas↑, CAPE (0-100 uM) is capable of inducing Fas signaling to promote p53 expression, leading to apoptotic cell death via Bax and caspase activation
P53↑,
BAX↑,
Casp↑,
β-catenin/ZEB1↓, anti-tumor activity of CAPE is mediated via reducing β-catenin levels
NDRG1↑, CAPE (30 uM) can promote NDRG1 expression via MAPK activation and down-regulation of STAT3
STAT3↓,
MAPK↑, CAPE stimulates mitogen-activated protein kinase (MAPK) and ERK
ERK↑,
eff↑, Res, thymoquinone and CAPE mediate lung tumor cell death via Bax upregulation and Bcl-2 down-regulation.
eff↑, co-administration of CA (100 Î¼M) and metformin (10 mM) is of interest in cervical squamous cell carcinoma therapy.
eff↑, in addition to CA, propolis contains other agents such as chrysin, p-coumaric acid and ferulic acid that are beneficial in tumor suppression.

1297-

CA,

Caffeic Acid Phenethyl Ester (CAPE) Induced Apoptosis in Serous Ovarian Cancer OV7 Cells by Deregulation of BCL2/BAX Genes

in-vitro,

Ovarian,

OV7

lysosome↓,
Apoptosis↑,
Bax:Bcl2↑,

5750-

CA,

Exploration of the anticancer properties of Caffeic Acid in malignant mesothelioma cells

in-vitro,

MM,

eff↑, CA exhibited greater efficiency than CINN in reducing cancer cell survival.
selectivity↑, This enhanced efficacy is primarily attributed to CA’s higher selectivity index and its ability to inhibit proliferation at lower concentrations.
Ki-67↓, CA suppressed proliferative markers, Ki67 and PCNA, inhibited colony formation and wound healing in MM cells.
PCNA↓,
TumCP↓,
p‑ERK↓, suppresses the phosphorylation of ERK1/2 and AKT proteins in a concentration-dependent manner
Akt↓,
p27↑, CA significantly enhanced the expression of p53-regulated proteins p21 and p27, resulting in G2/M arrest in both SPC111 and SPC212 cell lines.
P21↑,
TumCCA↑,
Bax:Bcl2↑, The increased Bax/Bcl-2 protein ratio, and BH3-only proteins (Bik and PUMA) and the cleavage of caspase-3 indicated that CA induces mitochondrial apoptosis.
cl‑Casp3↑,
mt-Apoptosis↑,

2019-

CAP,

Capsaicin: A Two-Decade Systematic Review of Global Research Output and Recent Advances Against Human Cancer

Review,

Var,

chemoPv↑, Capsaicin has shown significant prospects as an effective chemopreventive agent
Ca+2↑, Capsaicin was shown to cause upstream activation of Ca2+
antiOx↑, Another plausible mechanism implicated in the chemopreventive action of capsaicin is its anti-oxidative effects.
*ROS↓, capsaicin inhibits ROS release and the subsequent mitochondrial membrane potential collapse, cytochrome c expression, chromosome condensation, and caspase-3 activation induced by oxidized low-density lipoprotein in normal human HUVEC cells
*MMP∅,
*Cyt‑c∅,
*Casp3∅,
*eff↑, dietary curcumin and capsaicin concurrent administration in high-fat diet-fed rats were shown to mitigate the testicular and hepatic antioxidant status by increasing GSH levels, glutathione transferase activity, and Cu-ZnSOD expression
*Inflam↓, Anti-inflammation is another mechanism implicated in the chemopreventive action of capsaicin.
*NF-kB↓, inhibition of NF-kB by capsaicin
*COX2↓, compound elicits COX-2 enzyme activity inhibition and downregulation of iNOS
iNOS↓,
TRPV1↑, major pro-apoptotic mechanisms of capsaicin is via the vanilloid receptors, primarily TRPV1
i-Ca+2?, causing a concomitant influx of Ca2+: severe condition of mitochondria calcium overload. at high concentration (> 10 µM), capsaicin induces a slow but persistent increase in intracellular Ca2+
MMP↓, depolarization of mitochondria membrane potential
Cyt‑c↑, release of cytochrome C
Bax:Bcl2↑, activation of Bax and p53 through C-jun N-terminal kinase (JNK) activation
P53↑,
JNK↑,
PI3K↓, blocking the Pi3/Akt/mTOR signalling pathway, capsaicin increases levels of autophagic markers (LC3-II and Atg5)
Akt↓,
mTOR↓,
LC3II↑,
ATG5↑,
p62↑, enhances p62 and Fap-1 degradation and increases caspase-3 activity to induce apoptosis in human nasopharyngeal carcinoma cells
Fap1↓,
Casp3↑,
Apoptosis↑,
ROS↑, generation of ROS in human hepatoma (HepG2 cells)
MMP9↓, inhibition of MMP9 by capsaicin occurs via the suppression of AMPK-NF-κB, EGFR-mediated FAK/Akt, PKC/Raf/ERK, p38 MAPK, and AP-1 signaling pathway
eff↑, capsaicin 8% patch could promote the regeneration and restoration of skin nerve fibres in chemotherapy-induced peripheral neuropathy in addition to pain relief
eff↓, capsaicin has shown several unpleasant side effects, including stomach cramps, skin and gastric irritation, and burning sensation
eff↑, liposomes and micro-emulsion-based drugs have been known to significantly improve oral bioavailability and reduce the irritation of drugs
selectivity↑, In addition, these delivery systems can be surfaced-modified to perform site-directed/cell-specific drug delivery, thereby ensuring increased cell death of cancer cells while sparing non-selective normal cells
eff↑, Furthermore, owing to its antioxidant potential, capsaicin has been applied as a bioreduction and capping agent to synthesize biocompatible silver nanoparticles
ChemoSen↑, capsaicin has been combined with other anticancer therapies for more pronounced anticancer effects

5907-

CAR,

Anti-proliferative and pro-apoptotic effect of carvacrol on human hepatocellular carcinoma cell line HepG-2

in-vitro,

Liver,

HepG2

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

5897-

CAR,

Carvacrol Selectively Induces Mitochondria-Related Apoptotic Signaling in Primary Breast Cancer-Associated Fibroblasts

in-vitro,

BC,

Bax:Bcl2↑, marked increase in the BAX/BCL-XL ratio
PPARα↓, carvacrol reduced PPARα expression and NF-κB nuclear localization, increased SIRT1 and SIRT3 levels, selectively suppressed MMP-3
NF-kB↓,
SIRT1↑,
SIRT3↑,
MMP3↓,
selectivity↑, Carvacrol selectively targets breast cancer-associated fibroblasts by inducing mitochondria-related apoptotic signaling while largely sparing normal fibroblasts.
Bcl-2↓, In breast cancer lines, CV has been reported to down-regulate Bcl-2, up-regulate Bax, and induce caspase-3/-6/-9 activation in a dose-dependent manner, consistent with mitochondrial apoptosis
BAX↑,
Casp3↑,
Casp6↑,
Casp9↑,
mt-Apoptosis↑,

5895-

CAR,

Carvacrol as a Therapeutic Candidate in Breast Cancer: Insights into Subtype-Specific Cellular Modulation

in-vitro,

BC,

MCF-7

in-vitro,

BC,

MDA-MB-231

TumCG↓, Carvacrol reduced cell growth and migration, increased apoptosis by raising the BAX/BCL2 ratio, and lowered ROS levels, showing stronger antioxidant effects in MCF-7 cells.
TumCMig↓,
Apoptosis↑,
Bax:Bcl2↑,
ROS↓, 400 µM carvacrol treatment for 48 h reduced total ROS levels by ~2.8-fold in MCF-7 cells and ~1.3-fold in MDA-MB-231 cells
CD44↓, decreased CD44+ stem cell marker expression
CSCs↓,

6002-

CGA,

Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials

Review,

Var,

Review,

Diabetic,

Review,

AD,

Review,

Park,

Review,

Stroke,

*neuroP↑, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders,
*Inflam↓,
*antiOx↑,
*cardioP↑, Cardiovascular Protective Effect
*NRF2↑, pivotal antioxidants by activating the Nrf2 pathway
*AMPK↑, It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids.
*SOD↑, figure1
*Catalase↑,
*GSH↑,
*GPx↑,
*ROS↓,
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*COX2↓,
*glucose↓, CGA can attenuate glucose absorption
*TRPC1↓, CGA suppresses the levels of transient receptor potential canonical channel 1 (TRPC1) and decreases ROS and Ca2+, thus mitigating lysophosphatidylcholine (LPC)-induced endothelial injuries
*Ca+2↓,
*HO-1↑, enhancing superoxide dismutase (SOD), and producing NO and heme oxygenase (HO)-1
*NF-kB↓, CGAs can regulate NF-κB and PPARα pathways, lower HIF-1α expression, and suppress cardiac apoptotic signaling, thus executing beneficial effects against cardiac hypertrophy
*PPARα↝,
*Hif1a↓,
*JNK↓, CGA can inhibit NF-κB and JNK pathways, exhibiting cardioprotection
*BP↓, GCE (93 or 185 mg for 4 weeks) could lead to a reduction of 4.7 and 5.6 mmHg in levels of systolic blood pressure (SBP) and a decrease of 3.3 and 3.9 mmHg in levels of diastolic blood pressure (DBP)
*AntiDiabetic↑, CGA has shown its functions in protecting β cells from apoptosis, improving β cell function, facilitating glycemic control, and mitigating DM complications.
*hepatoP↑, CGA can mediate hepatoprotective roles in various pathological conditions of the liver via antioxidant and anti-inflammatory features
*TLR4↓, (1) It can inhibit TLR4-mediated activation of NF-κB, thus suppressing pro-inflammatory responses;
*NRF2↑, (3) it can increase the activity of the Nrf2 pathway
*Casp↓, (4) it can inhibit caspases’ activation to suppress hepatic apoptosis induced by chemicals or toxins.
*neuroP↑, CGA has shown diverse neuroprotective effects on various neuropathological conditions which may be exerted through inhibition of neuroinflammation, reduction in ROS production, prevention of oxidation, and suppression of neuronal apoptosis
*Aβ↓, CGA or extracts containing CGA can inhibit Aβ aggregation-caused cellular injury in SH-SY5Y cells, a neuroblastoma cell line
*LDH↓, CGA increases survival and decreases apoptosis via decreasing activities of lactate dehydrogenase (LDH) and the levels of MDA and raising the levels of SOD and GSH-Px
*MDA↓,
*memory↑, CGA prevents Aβ deposition and neuronal loss and ameliorates learning and memory deterioration in APP/PS2 mice
*AChE↓, CGA inhibits acetylcholinesterase (AChE) activity in rat brains, suggesting its beneficial effect against cognitive impairment
*eff↑, CGA protects against injury caused by cerebral ischemia/reperfusion
EMT↝, It also modulates the epithelial–mesenchymal transition (EMT) process of breast cancer cells by downregulation of N-cadherin and upregulation of E-cadherin
N-cadherin↓,
E-cadherin↑,
TumCCA↑, CGA can stall the cells in the S phase and cause DNA injury in human colon cancer cell lines such as HCT116 and HT29 by increasing ROS production, upregulation of phosphorylated p53, HO-1, and Nrf2
ROS↑,
p‑P53↑,
HO-1↑,
NRF2↑,
ChemoSen↑, CGA in combination with doxorubicin suppresses cellular metabolic activity, colony formation, and cell growth of U2OS and MG-63 cells by upregulating caspase-3 and PARP and suppressing the p44/42 MAPK pathway, thus inducing apoptosis
mtDam↑, mechanism involves CGA-mediated excessive ROS production, causing mitochondrial dysfunction, leading to increases in cleaved levels of caspase-3, caspase-9, PARP, and Bax/Bcl-2 ratio
Casp3↑,
Casp9↑,
PARP↑,
Bax:Bcl2↑,
TumCG↓, in vivo experiments showing that CGA can reduce tumor growth and volume in pancreatic cancer cell-bearing nude mice by modifying cancer cell metabolism through decreasing levels of cyclin D1, c-Myc, and cyclin-dependent kinase-2 (CDK-2),
cycD1/CCND1↓,
cMyc↓,
CDK2↓,
mitResp↓, interrupting mitochondrial respiration, and suppressing aerobic glycolysis
Glycolysis↓,
Hif1a↓, CGA arrests cells at the phase of G1 and inhibits cell viability of prostate cancer cell DU145 by suppressing the levels of HIF-1α and SPHK-1, PCNA, cyclin-D, CDK-4, p-Akt, p-GSK-3β, and VEGF
PCNA↓,
p‑GSK‐3β↓,
VEGF↓,
PI3K↓, inhibition of the PI3K/Akt/mTOR pathway
Akt↓,
mTOR↓,
OS↑, Extending Lifespan in Worms

4772-

CoQ10,

The anti-tumor activities of coenzyme Q0 through ROS-mediated autophagic cell death in human triple-negative breast cells

in-vitro,

BC,

MDA-MB-468

 IC50 values of 4.8, 7.6, and 20.6 µM

in-vitro,

BC,

MDA-MB-231

TumCP↓, Coenzyme Q0 (CoQ0) inhibits proliferation and colony formation in MDA-MB-468 and 231 cells.
Apoptosis↑, CoQ0 induced apoptosis associated with caspase-3 activation and PARP cleavage
Casp3↑,
cl‑PARP↑,
LC3II↑, CoQ0 induced autophagic cell death is accompanied by LC3-II accumulation and AVO formation
eff↓, Antioxidant NAC prevents CoQ0-induced apoptosis and autophagy.
TumCG↓, CoQ0 (Fig. 1A) suppressed TNBC and Hs578T cell growth, as well as dose-dependently reduced cell growth.
Bax:Bcl2↑, CoQ0 increases Bax/Bcl-2 and Beclin-1/Bcl-2 ratio in both TNBC cell lines
Beclin-1↑,
TumAuto↑, CoQ0 induces autophagy, which ultimately results in cell death TNBC cells
ROS↑, CoQ0 activates intracellular ROS generation in TNBC cells. TNBC cells treated with CoQ0 (5 or 7.5 µM for 0–120 min) showed substantially elevated ROS accumulation

4776-

CoQ10,

Antitumor properties of Coenzyme Q0 against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy

vitro+vivo,

Ovarian,

SKOV3

(SKOV-3) cells and xenografted nude mice

ROS↑, CoQ0 triggered intracellular ROS production, whereas antioxidant N-acetylcysteine prevented CoQ0-induced apoptosis, but not autophagy
eff↓, whereas antioxidant NAC N-acetylcysteine prevented CoQ0-induced apoptosis, but not autophagy
AntiCan↑, Furthermore, CoQ0 treatment to SKOV-3 xenografted nude mice reduced tumor incidence and burden
Apoptosis↑, Our findings emphasize that CoQ0 triggered ROS-mediated apoptosis and cytoprotective autophagy.
tumCV↓, CoQ0 inhibits viability and growth of human ovarian carcinoma cells
TumCG↓, CoQ0 suppresses tumor growth in SKOV-3 xenografted nude mice
TumCCA↑, CoQ0 induces G2/M cell-cycle arrest and reduces cell-cycle proteins in SKOV-3 cells
LC3s↑, CoQ0 promotes LC3 accumulation and AVOs formation in SKOV-3 cells
ERStress↑, CoQ0 triggers apoptotic death of SKOV-3 cells via mitochondrial and ER-stress signals
Beclin-1↑, CoQ0 increases Beclin-1/Bcl-2 and Bax/Bcl-2, and inhibits HER-2/neu/AKT/mTOR signalling in SKOV-3 cells
Bax:Bcl2↑,
HER2/EBBR2↓,
Akt↓,
mTOR↓,

1981-

CUR,

Mitochondrial targeted curcumin exhibits anticancer effects through disruption of mitochondrial redox and modulation of TrxR2 activity

in-vitro,

Lung,

eff↑, Mitocurcumin, showed 25-50 fold higher efficacy in killing lung cancer cells as compared to curcumin
ROS↑, Mitocurcumin increased the mitochondrial reactive oxygen species (ROS
mt-GSH↓, decreased the mitochondrial glutathione levels
Bax:Bcl2↑, increased BAX to BCL-2 ratio
Cyt‑c↑, cytochrome C release into the cytosol
MMP↓, loss of mitochondrial membrane potential
Casp3↑, increased caspase-3 activity
Trx2↓, mitocurcumin revealed that it binds to the active site of the mitochondrial thioredoxin reductase (TrxR2) with high affinity
TrxR↓, In corroboration with the above finding, mitocurcumin decreased TrxR activity in cell free as well as the cellular system.
mt-DNAdam↑, mitochondrial DNA damage

CUR,

Curcumin Suppresses Malignant Glioma Cells Growth and Induces Apoptosis by Inhibition of SHH/GLI1 Signaling Pathway in Vitro and Vivo

vitro+vivo,

MG,

U87MG

 15uM

vitro+vivo,

MG,

T98G

 31uM
31 uM

HH↓, Both mRNA and protein levels of SHH/GLI1 signaling (Shh, Smo, GLI1) were downregulated in a dose‐ and time‐dependent manner
Shh↓, inhibition of SHH/GLI1 signaling by curcumin may act as a novel mechanism of the apoptosis.
Gli1↓,
cycD1/CCND1↓,
Bcl-2↓,
FOXM1↓,
Bax:Bcl2↑, The Bax/Bcl‐2 ratio (Figure 6D) also gradually increased.
TumCP↓, Curcumin suppressed cell proliferation, colony formation, migration, and induced apoptosis which was mediated partly through the mitochondrial pathway after an increase in the ratio of Bax to Bcl2.
TumCMig↓,
Apoptosis↑,
TumVol↑, Intraperitoneal injection of curcumin in vivo reduced tumor volume,
TumCCA↑, Curcumin Inhibited Proliferation of Human Glioma Cells and induced G2/M Arrest
Casp3↑, level of caspase‐3 increases significantly after curcumin treatment.
OS↑, Curcumin Inhibited GBM Growth in Vivo through SHH/GLI1 Signaling and Prolonged the Survival Period

1605-

EA,

Ellagic Acid and Cancer Hallmarks: Insights from Experimental Evidence

Review,

Var,

*BioAv↓, Within the gastrointestinal tract, EA has restricted bioavailability, primarily due to its hydrophobic nature and very low water solubility.
antiOx↓, strong antioxidant properties [12,13], anti-inflammatory effects
Inflam↓,
TumCP↓, numerous studies indicate that EA possesses properties that can inhibit cell proliferation
TumCCA↑, achieved this by causing cell cycle arrest at the G1 phase
cycD1/CCND1↓, reduction of cyclin D1 and E levels, as well as to the upregulation of p53 and p21 proteins
cycE/CCNE↓,
P53↑,
P21↑,
COX2↓, notable reduction in the protein expression of COX-2 and NF-κB as a result of this treatment
NF-kB↓,
Akt↑, suppressing Akt and Notch signaling pathways
NOTCH↓,
CDK2↓,
CDK6↓,
JAK↓, suppression of the JAK/STAT3 pathway
STAT3↓,
EGFR↓, decreased expression of epidermal growth factor receptor (EGFR)
p‑ERK↓, downregulated the expression of phosphorylated ERK1/2, AKT, and STAT3
p‑Akt↓,
p‑STAT3↓,
TGF-β↓, downregulation of the TGF-β/Smad3
SMAD3↓,
CDK6↓, EA demonstrated the capacity to bind to CDK6 and effectively inhibit its activity
Wnt/(β-catenin)↓, ability of EA to inhibit phosphorylation of EGFR
Myc↓, Myc, cyclin D1, and survivin, exhibited decreased levels
survivin↓,
CDK8↓, diminished CDK8 level
PKCδ↓, EA has demonstrated a notable downregulatory impact on the expression of classical isoenzymes of the PKC family (PKCα, PKCβ, and PKCγ).
tumCV↓, EA decreased cell viability
RadioS↑, further intensified when EA was combined with gamma irradiation.
eff↑, EA additionally potentiated the impact of quercetin in promoting the phosphorylation of p53 at Ser 15 and increasing p21 protein levels in the human leukemia cell line (MOLT-4)
MDM2↓, finding points to the ability of reduced MDM2 levels
XIAP↓, downregulation of X-linked inhibitor of apoptosis protein (XIAP).
p‑RB1↓, EA exerted a decrease in phosphorylation of pRB
PTEN↑, EA enhances the protein phosphatase activity of PTEN in melanoma cells (B16F10)
p‑FAK↓, reduced phosphorylation of focal adhesion kinase (FAK)
Bax:Bcl2↑, EA significantly increases the Bax/Bcl-2 rati
Bcl-xL↓, downregulates Bcl-xL and Mcl-1
Mcl-1↓,
PUMA↑, EA also increases the expression of Bcl-2 inhibitory proapoptotic proteins PUMA and Noxa in prostate cancer cells
NOXA↑,
MMP↓, addition to the reduction in MMP, the release of cytochrome c into the cytosol occurs in pancreatic cancer cells
Cyt‑c↑,
ROS↑, induction of ROS production
Ca+2↝, changes in intracellular calcium concentration, leading to increased levels of EndoG, Smac/DIABLO, AIF, cytochrome c, and APAF1 in the cytosol
Endoglin↑,
Diablo↑,
AIF↑,
iNOS↓, decreased expression of Bcl-2, NF-кB, and iNOS were observed after exposure to EA at concentrations of 15 and 30 µg/mL
Casp9↑, increase in caspase 9 activity in EA-treated pancreatic cancer cells PANC-1
Casp3↑, EA-induced caspase 3 activation and PARP cleavage in a dose-dependent manner (10–100 µmol/L)
cl‑PARP↑,
RadioS↑, EA sensitizes and reduces the resistance of breast cancer MCF-7 cells to apoptosis induced by γ-radiation
Hif1a↓, EA reduced the expression of HIF-1α
HO-1↓, EA significantly reduced the levels of two isoforms of this enzyme, HO-1, and HO-2, and increased the levels of sEH (Soluble epoxide hydrolase) in LnCap
HO-2↓,
SIRT1↓, EA-induced apoptosis was associated with reduced expression of HuR and Sirt1
selectivity↑, A significant advantage of EA as a potential chemopreventive, anti-tumor, or adjuvant therapeutic agent in cancer treatment is its relative selectivity
Dose∅, EA significantly reduced the viability of cancer cells at a concentration of 10 µmol/L, while in healthy cells, this effect was observed only at a concentration of 200 µmol/L
NHE1↓, EA had the capacity to regulate cytosolic pH by downregulating the expression of the Na+/H+ exchanger (NHE1)
Glycolysis↓, led to intracellular acidification with subsequent impairment of glycolysis
GlucoseCon↓, associated with a decrease in the cellular uptake of glucose
lactateProd↓, notable reduction in lactate levels in supernatant
PDK1?, inhibit pyruvate dehydrogenase kinase (PDK) -bind and inhibit PDK3
PDK1?,
ECAR↝, EA has been shown to influence extracellular acidosis
COX1↓, downregulation of cancer-related genes, including COX1, COX2, snail, twist1, and c-Myc.
Snail↓,
Twist↓,
cMyc↓,
Telomerase↓, EA, might dose-dependently inhibit telomerase activity
angioG↓, EA may inhibit angiogenesis
MMP2↓, EA demonstrated a notable reduction in the secretion of matrix metalloproteinase (MMP)-2 and MMP-9.
MMP9↓,
VEGF↓, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
Dose↝, At lower concentrations (10 and 20 μM), EA led to a substantial increase in VEGF levels. However, at higher doses (40 and 100 μM), a notable reduction in VEGF
PD-L1↓, EA downregulated the expression of the immune checkpoint PD-L1 in tumor cells
eff↑, EA might potentially enhance the efficacy of anti-PD-L1 treatment
SIRT6↑, EA exhibited statistically significant upregulation of sirtuin 6 at the protein level in Caco2 cells
DNAdam↓, increase in DNA damage

1620-

EA,

Rad,

Radiosensitizing effect of ellagic acid on growth of Hepatocellular carcinoma cells: an in vitro study

in-vitro,

Liver,

HepG2

ROS↑, Treatment of HepG2 cells with EA and gamma radiation showed increased reactive oxygen species generation
P53↑, up regulation of p53 protein expression
TumCCA↑, combination treatment increased G2/M phase cell population
IL6↓, decreased IL-6, COX–2 and TNF-α expression
COX2↓,
TNF-α↓,
MMP↓, caused a loss in mitochondrial membrane potential
angioG↓, decreased level of angiogenesis marker MMP-9
MMP9↓,
BAX↑,
Casp3↑,
Apoptosis↑,
RadioS↑,
TBARS↑, EA increased TBARS level in HepG2 cells after irradiation
GSH↓, EA decreased the reduced glutathione content in HepG2 cells after irradiation
Bax:Bcl2↑, Combination treatment increased the Bax/Bcl2 ratio
p‑NF-kB↓, EA along with radiation decreased p-NF-κB level in tumour cells
p‑STAT3↓, Radiation and EA combination treatment decreased p-STAT3 level in tumour cells

1606-

EA,

Ellagic acid inhibits proliferation and induced apoptosis via the Akt signaling pathway in HCT-15 colon adenocarcinoma cells

in-vitro,

Colon,

HCT15

20-120 uM

TumCP↓,
cycD1/CCND1↓,
Apoptosis↑,
PI3K↓, strong inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt pathway by EA
Akt↓,
ROS↑, production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with EA
Casp3↑, EA promoted the expression of Bax, caspase-3, and cytochrome c, and suppression of Bcl-2 activity in HCT-15 cells
Cyt‑c↑,
Bcl-2↓,
TumCCA↑, induces G2/M phase cell cycle arrest in HCT-15 cells
Dose∅, since 60 lM of the drug concentration could cause attentional loss of cells (60 and 45 % were viable in 12 and 24 h treatment, respectively) for crucial experiments, we used this dosage to assess the effect of EA in killing HCT-15 cells
ALP↓, significant decrease in the activity of ALP at 60 lM concentration of EA for the 12 h treatment
LDH↓, decrease in the activity of LDH in cells was proportional to increase in the incubation time with EA.
PCNA↓, EA down-regulated the expressions of PCNA and cyclin D1
P53↑, EA promoted p53 gene expression
Bax:Bcl2↑, increase in the Bcl-2/Bax ratio

26-

EGCG,

QC,

docx,

Green tea and quercetin sensitize PC-3 xenograft prostate tumors to docetaxel chemotherapy

vitro+vivo,

Pca,

PC3

BAD↓,
cl‑PARP↑,
Casp7↑,
IκB↓,
Ki-67↓,
VEGF↓,
EGFR↓,
FGF↓,
TGF-β↓,
TNF-α↓,
SCF↓,
Bax:Bcl2↑,
NF-kB↓,
chemoP↑, This study provides a novel regimen to enhance the therapeutic effect of Doc in a less-toxic manner and reduce its risk of side effects in treatment of CRPC.
ChemoSen↑, GT and Q with LD Doc significantly enhanced the potency of Doc 2-fold and reduced tumor growth by 62 % compared to LD Doc in 7-weeks intervention.
TumVol↓,

1332-

EMD,

Induction of Apoptosis in HepaRG Cell Line by Aloe-Emodin through Generation of Reactive Oxygen Species and the Mitochondrial Pathway

in-vivo,

Nor,

HepaRG

rata

*tumCV↓,
*ROS↑,
*MMP↓,
*Fas↑,
*P53↑,
*P21↑,
*Bax:Bcl2↑,
*Casp3↑,
*Casp8↑,
*Casp9↑,
*cl‑PARP↑,
*TumCCA↑, S-phase cell cycle arrest
*P21↑,
*cycE/CCNE↑,
*cycA1/CCNA1↓,
*CDK2↓,

1321-

EMD,

Antitumor effects of emodin on LS1034 human colon cancer cells in vitro and in vivo: roles of apoptotic cell death and LS1034 tumor xenografts model

in-vitro,

CRC,

LS1034

in-vivo,

NA,

mice

tumCV↓,
TumCCA↑, induced G2/M phase arrest
ROS↑,
Ca+2↑,
MMP↓,
Apoptosis↑,
Cyt‑c↑,
Casp9↑,
Bax:Bcl2↑,

Showing Research Papers: 1 to 50 of 95
Page 1 of 2 Next

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 95

Pathway results for Effect on Cancer / Diseased Cells:

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

antiOx↑, 5, Catalase↑, 1, GPx↑, 1, GSH↑, 1, HO-1↑, 1, MDA↓, 1, NRF2↑, 2, ROS↓, 4, ROS↑, 1, SOD↑, 1,

Mitochondria & Bioenergetics ⓘ

MMP↓, 1, MMP∅, 1,

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1, glucose↓, 1, LDH↓, 1, PPARα↝, 1,

Cell Death ⓘ

Bax:Bcl2↑, 1, Casp↓, 1, Casp3↑, 1, Casp3∅, 1, Casp8↑, 1, Casp9↑, 1, Cyt‑c∅, 1, Fas↑, 1, JNK↓, 1, MAPK↓, 1,

Transcription & Epigenetics ⓘ

tumCV↓, 1,

Protein Folding & ER Stress ⓘ

HSP70/HSPA5↑, 1,

DNA Damage & Repair ⓘ

P53↑, 1, cl‑PARP↑, 1,

Cell Cycle & Senescence ⓘ

CDK2↓, 1, cycA1/CCNA1↓, 1, cycE/CCNE↑, 1, P21↑, 2, TumCCA↑, 1,

Migration ⓘ

AntiAg↑, 1, Ca+2↓, 1, LAMs↑, 1, PKCδ↓, 1, Smad1↑, 1, TRPC1↓, 1,

Angiogenesis & Vasculature ⓘ

angioG↓, 1, Hif1a↓, 1,

Immune & Inflammatory Signaling ⓘ

COX2↓, 2, IL6↓, 1, Inflam↓, 6, NF-kB↓, 3, TLR4↓, 1, TNF-α↓, 1,

Synaptic & Neurotransmission ⓘ

AChE↓, 2,

Protein Aggregation ⓘ

Aβ↓, 1,

Drug Metabolism & Resistance ⓘ

BioAv↓, 2, eff↑, 2, Half-Life∅, 1,

Clinical Biomarkers ⓘ

BP↓, 1, IL6↓, 1, LDH↓, 1,

Functional Outcomes ⓘ

AntiDiabetic↑, 1, cardioP↑, 1, hepatoP↑, 2, memory↑, 1, neuroP↑, 2, toxicity↓, 2,

Infection & Microbiome ⓘ

Bacteria↓, 1,
Total Targets: 64

Scientific Paper Hit Count for: Bax:Bcl2, Bax:Bcl2 ratio

8 Thymoquinone
7 Apigenin (mainly Parsley)
6 Berberine
6 Emodin
6 Sulforaphane (mainly Broccoli)
5 Baicalein
4 Quercetin
4 Lycopene
3 EGCG (Epigallocatechin Gallate)
3 Curcumin
3 Caffeic acid
3 Carvacrol
3 Ellagic acid
2 Cisplatin
2 Silver-NanoParticles
2 Arctigenin
2 Docetaxel
2 Berbamine
2 Propolis -bee glue
2 Coenzyme Q10
2 Gambogic Acid
2 Garcinol
2 Graviola
2 Myricetin
1 2-DeoxyGlucose
1 Astragalus
1 Allicin (mainly Garlic)
1 Alpha-Lipoic-Acid
1 Andrographis
1 Ashwagandha(Withaferin A)
1 Ascorbyl Palmitate
1 Paclitaxel
1 Betulinic acid
1 Boswellia (frankincense)
1 Capsaicin
1 Chlorogenic acid
1 Radiotherapy/Radiation
1 Ferulic acid
1 Gallic acid
1 Hydroxycinnamic-acid
1 HydroxyTyrosol
1 Juglone
1 Luteolin
1 Magnolol
1 Plumbagin
1 Rosmarinic acid
1 salinomycin
1 doxorubicin
1 Thymol-Thymus vulgaris
1 Vitamin D3
1 Melatonin

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

Bax:Bcl2 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 ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

Infection & Microbiome ⓘ

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