Bak Cancer Research Results

Bak, BAK or BAK1: Click to Expand ⟱
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Bak (also known as BAK or BAK1) is a protein that plays a crucial role in regulating cell death.
In cancer, the Bak protein is often inactivated or downregulated, allowing cancer cells to evade apoptosis and continue to proliferate uncontrollably.
Scientific Papers found: Click to Expand⟱
4388- AgNPs,    Differential Cytotoxic Potential of Silver Nanoparticles in Human Ovarian Cancer Cells and Ovarian Cancer Stem Cells
- in-vitro, Cerv, NA
tumCV↓, the numbers of A2780 (bulk cells) and ALDH+/CD133+ colonies were significantly reduced
CSCs↓,
selectivity↑, induced apoptosis in pancreatic CSCs and cancer cell lines, but had no effect on human normal pancreatic epithelial cells
Apoptosis↑,
ROS↑, figure 5, AgNPs induces apoptosis by oxidative stress
LDH↓, figure 5 (leakage outside the cell increases)
Casp3↑, AgNPs treated cells shows up-regulation of caspase-3, bax, bak, and c-myc, genes
BAX↑,
Bak↑,
cMyc↑,
MMP↓, and loss of mitochondrial membrane potential.

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

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

3155- Ash,    Overview of the anticancer activity of withaferin A, an active constituent of the Indian ginseng Withania somnifera
- Review, Var, NA
Half-Life↝, The pharmacokinetic study demonstrates that a dose of 4 mg/kg in mice results in 2 μM concentration in plasma (with a half-life of 1.3 h, in the breast cancer model of mice),
Inflam↓, WA has many biological activities: anti-inflammatory (Dubey et al. 2018), immunomodulatory (Davis and Girija 2000), antistress (Singh et al. 2016), antioxidant (Sumathi et al. 2007) and anti-angiogenesis
antiOx↓,
angioG↓,
ROS↑, WA induces oxidative stress (ROS) determining mitochondrial dysfunction as well as apoptosis in leukaemia cells
BAX↑, withaferin mediates apoptosis by ROS generation and activation of Bax/Bak.
Bak↑,
E6↓, The results of the study show that withaferin treatment downregulates the HPV E6 and E7 oncoprotein and induces accumulation of p53 result in the activation of various apoptotic markers (e.g. Bcl2, Bax, caspase-3 and cleaved PARP).
E7↓,
P53↑,
Casp3↑,
cl‑PARP↑,
STAT3↓, WA treatment also decreases the level of STAT3
eff↑, This study concludes that combination of DOX with WA can reduce the doses and side effects of the treatment which gives valuable possibilities for future research.
HSP90↓, by inhibiting the HSP90
TGF-β↓, WA inhibited TGFβ1 and TNFα- induced EMT;
TNF-α↓,
EMT↑,
mTOR↓, by downregulation of mTOR/STAT3 signalling.
NOTCH1↓, WA showed inhibition of pro-survival signalling markers (Notch1, pAKT and NFκB)
p‑Akt↓,
NF-kB↓,
Dose↝, WA dose escalation sets consisted of 72, 108, 144 and 216 mg, fractioned in 2-4 doses/day.

1355- Ash,    Withaferin A-Induced Apoptosis in Human Breast Cancer Cells Is Mediated by Reactive Oxygen Species
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MCF-7 - in-vitro, Nor, HMEC
eff↑, WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). ****
mt-ROS↑, WA-induced apoptosis in human breast cancer cells is mediated by mitochondria-derived ROS
mitResp↓,
OXPHOS↓, WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity.
compIII↑,
BAX↑,
Bak↑,
other↓, Cu,Zn-Superoxide dismutase (Cu,Zn-SOD) overexpression confers protection against WA-induced ROS production and apoptosis
ATP∅, steady-state levels of ATP were unaffected by WA treatment in either cell line
*ROS∅, but not in a normal human mammary epithelial cell line (HMEC). WA treatment caused ROS production in breast cancer cells, HMEC were resistant to pro-oxidant effect of this agent.

1360- Ash,  immuno,    Withaferin A Increases the Effectiveness of Immune Checkpoint Blocker for the Treatment of Non-Small Cell Lung Cancer
- in-vitro, Lung, H1650 - in-vitro, Lung, A549 - in-vitro, CRC, HCT116 - in-vitro, BC, MDA-MB-231 - in-vivo, NA, NA
PD-L1↑,
eff↓, The administration of N-acetyl cysteine (NAC), a reactive oxygen species (ROS) scavenger, abrogated WFA-induced ICD and PD-L1 upregulation, suggesting the involvement of ROS in this process.
ROS↑,
ER Stress↑,
Apoptosis↑,
BAX↑,
Bak↑,
BAD↑,
Bcl-2↓,
XIAP↓,
survivin↓,
cl‑PARP↑,
CHOP↑,
p‑eIF2α↑, phosphorylation of the eukaryotic initiation factor eIF-2
ICD↑,
eff↑, WFA Sensitizes LLC Syngeneic Mouse Tumors to α-PD-L1 In Vivo

1398- BBR,    Berberine inhibits the progression of renal cell carcinoma cells by regulating reactive oxygen species generation and inducing DNA damage
- in-vitro, Kidney, NA
TumCP↓,
TumCMig↓,
ROS↑,
Apoptosis↑,
BAX↑,
BAD↑,
Bak↑,
Cyt‑c↑,
cl‑Casp3↑,
cl‑Casp9↑,
E-cadherin↑,
TIMP1↑,
γH2AX↑,
Bcl-2↓,
N-cadherin↓,
Vim↓,
Snail↓,
RAD51↓,
PCNA↓,

5842- CAP,    Capsaicin: Current Understanding of Its Mechanisms and Therapy of Pain and Other Pre-Clinical and Clinical Uses
- Review, Nor, NA - Review, Diabetic, NA
*Pain↓, capsaicin promotes pain relief when used in the right dosage and frequency.
*TRPV1↑, capsaicin-induced pain is also used to assess new molecules that target TRPV1 receptor. Capsaicin activates TRPV1
AMPK↑, The inhibitory effect of capsaicin on this process seems to involve the activation of 5’ adenosine monophosphate-activated protein kinase (AMPK) in conjunction with intracellular ROS release
ROS↑,
TumCP↑, AMPK activation is also linked to inhibition of cell proliferation and apoptosis [153,154]
Apoptosis↑,
TumCCA↑, capsaicin targets preadipocyte proliferation by blocking the S-phase of the cell cycle [149].
Casp3↑, capsaicin induces apoptosis in preadipocytes via the activation of caspase-3, Bax, and Bak, cleavage of PARP, and down-regulation of Bcl-2
BAX↑,
Bak↑,
cl‑PARP↑,
Bcl-2↓,
RNS↑, capsaicin induces apoptosis in BMSC via increased production of ROS and reactive nitrogen species (RNS) [
*glucose↓, healthy male volunteers revealed that capsaicin lowers glucose and increases insulin levels shortly after oral administration
*Insulin↑,
*BP↓, Capsaicin stimulates the release of CGRP through the activation of TRPV1 and therefore decreases blood pressure
*AntiAg↑, Capsaicin has been shown to inhibit platelet aggregation [199,200], which may also provide protection against cardiovascular diseases
ER Stress↑, endoplasmic reticulum stress in human nasopharyngeal carcinoma and pancreatic cancer cells,
Hif1a↓, capsaicin increases the degradation of hypoxia inducible factor 1α in non-small cell lung cancer,
chemoPv↑, mounting evidence supporting a chemo-preventive role for capsaicin in cancer cell culture and animal models,

1517- CAP,    Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1)
- in-vitro, Bladder, TSGH8301 - in-vitro, CRC, T24/HTB-9
ENOX2↓, capsaicin downregulates tNOX expression
TumCCA↑, Capsaicin Downregulates tNOX and Induces Cell Cycle Arrest at G1 Phase
ERK↓, inhibit the activation of ERK
p‑FAK↓,
p‑pax↓,
TumCMig↓,
EMT↓,
SIRT1↓, downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells
Dose∅, 100 and 200 μM effectively reduced tNOX expression in bladder cancer TSGH8301 and T24
ROS↑, capsaicin dose-dependently increased ROS generation
MMP↓,
Bcl-2↓,
Bak↑,
cl‑PARP↑,
Casp3↑,
SIRT1↓, 100 and 200 μM capsaicin decreased SIRT1 expression
ac‑P53↑, concurrently increased p53 acetylation
BIM↑, enhanced the expression level of Bim
p‑RB1↓, downregulation of phosphorylated Rb and cyclin D,
cycD1/CCND1↓,
Dose∅, Interestingly, cell migration was somewhat increased with 10 μM accompanied by up-regulation of tNOX expression
β-catenin/ZEB1↓,
N-cadherin↓,
E-cadherin↑,

2780- CHr,    Anti-cancer Activity of Chrysin in Cancer Therapy: a Systematic Review
- Review, Var, NA
*antiOx↑, antioxidant (13), anti-inflammatory (14), antibacterial (15), anti-hypertensive (16), anti-allergic (17), vasodilator (18),
Inflam↓,
*hepatoP↑, anti-diabetic (19), anti-anxiety (10), anti-viral (20), anti-estrogen (21), liver protective (22), anti-aging (23), anti-seizure (24), and anti-cancer effects (25)
AntiCan↑,
Cyt‑c↑, (1) facilitating the release of cytochrome C from the mitochondria,
Casp3↑, (2) activating caspase-3 and inhibiting the activity of the XIAP molecule,
XIAP↓,
p‑Akt↓, (3) reducing AKT phosphorylation and triggering the PI3K pathway and induction of apoptosis
PI3K↑,
Apoptosis↑,
COX2↓, chrysin interacts weakly with COX-1 binding site whereas displayed a remarkable interaction with COX-2.
FAK↓, ESCC cells: resultant blockage of the FAK/AKT signaling pathways
AMPK↑, A549: activation of AMPK by chrysin contributes to Akt suppression
STAT3↑, 4T1cell: inhibited STAT3 activation
MMP↓, Chrysin induces apoptosis through the intrinsic mitochondrial pathway that disrupts mitochondrial membrane potential (MMP) and increases DNA fragmentation.
DNAdam↑,
BAX↑, produces pro-apoptotic proteins, including Bax and Bak, and activates caspase-9 and caspase-3 in various cancer cells
Bak↑,
Casp9↑,
p38↑, chrysin can inhibit tumor growth by activating P38 MAPK and stopping the cell cycle
MAPK↑,
TumCCA↑,
ChemoSen↑, beneficial in inhibiting chemotherapy resistance of cancer cells
HDAC8↓, chrysin suppresses tumorigenesis by inhibiting histone deacetylase 8 (HDAC8)
Wnt↓, chrysin can attenuate Wnt and NF-κB signaling pathways
NF-kB↓,
angioG↓, chrysin can inhibit angiogenesis and inducing apoptosis in HTh7 cells, 4T1 mice, and MDA-MB-231 cells
BioAv↓, low bioavailability of flavonoids such as chrysin

424- CUR,    Curcumin inhibits autocrine growth hormone-mediated invasion and metastasis by targeting NF-κB signaling and polyamine metabolism in breast cancer cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Src↓,
p‑STAT1↓, pSTAT-1
p‑Akt↓,
p‑p44↓, p-p44
p‑p42↓, p-p42
RAS↓,
Raf↓, c-RAF
Vim↓,
β-catenin/ZEB1↓,
P53↓,
Bcl-2↓,
Mcl-1↓,
PIAS-3↑,
SOCS-3↑,
SOCS1↑,
ROS↑,
NF-kB↓, NF-kB inactivation, ROS generation and PA depletion in MCF-7, MDA-MB-453 and MDA-MB-231 breast can- cer cells
PAO↑,
SSAT↑,
P21↑,
Bak↑,

4826- CUR,    The Bright Side of Curcumin: A Narrative Review of Its Therapeutic Potential in Cancer Management
- Review, Var, NA
*antiOx↑, Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators
*Inflam↑,
*ROS↓,
Apoptosis↑, Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers
TumCP↓,
BioAv↓, application is limited by its poor bioavailability due to its rapid metabolism and low absorption.
Half-Life↓,
eff↑, curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy.
TumCCA↑, Studies have demonstrated that curcumin can suppress the proliferation of cancer cells by interfering with the cell cycle [21,22]
BAX↑, Curcumin enhances the expression of pro-apoptotic proteins such as Bax, Bak, PUMA, Bim, and Noxa and death receptors such as TRAIL-R1/DR4 and TRAIL-R2/DR5
Bak↑,
PUMA↑,
BIM↑,
NOXA↑,
TRAIL↑,
Bcl-2↓, curcumin decreases the levels of anti-apoptotic proteins like Bcl-2, Bcl-XL, survin, and XIAP
Bcl-xL↓,
survivin↓,
XIAP↓,
cMyc↓, This shift in the balance of apoptotic regulators facilitates the release of cytochrome c from mitochondria [33,35] and activates caspases
Casp↑,
NF-kB↓, Curcumin suppresses the activity of key transcription factors like NF-κB, STAT3, and AP-1 and interferes with critical signal transduction pathways such as PI3K/Akt/mTOR and MAPK/ERK.
STAT3↓,
AP-1↓,
angioG↓, curcumin inhibits angiogenesis and metastasis by downregulating VEGF, VEGFR2, and matrix metalloproteinases (MMPs).
TumMeta↑,
VEGF↓,
MMPs↓,
DNMTs↓, Epigenetic modifications through the inhibition of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs) further contribute to its anticancer properties.
HDAC↓,
ROS↑, curcumin-loaded nanoparticles showed significant cytotoxicity in the SCC25, MDA-MB-231, and A549 cell lines, with a decrease in tumor cell proliferation, an increase in ROS, and an increase in apoptosis.

2263- dietMet,    Methionine Restriction and Cancer Biology
- Review, Var, NA
AntiCan↑, dependence of many tumor cells on an exogenous source of the sulfur amino acid, methionine, [9,10,11] makes dietary methionine restriction (MR) an exciting potential tool in the treatment of cancer.
TumCP↓, Proliferation and growth of several types of cancer cells are inhibited by MR,
TumCG↓,
selectivity↑, while normal cells are unaffected by limiting methionine as long as homocysteine is present
ChemoSen↓, MR has been shown to enhance efficacy of chemotherapy and radiation therapy in animal models
RadioS↑,
Insulin↓, MR may work by inhibiting prostate cancer cell proliferation, inhibiting the insulin/IGF-1 axis
*GlucoseCon↑, increase in tissue-specific glucose uptake measured during a hyperinsulinemic-euglycemic clamp
*ROS↓, MR does not increase oxidative stress, in part because MR enhances antioxidant capacity and increases proton leak in the liver, likely decreasing ROS production
*antiOx↑,
*GSH↑, ability of MR to increase GSH levels in red blood cells. Surprisingly, when methionine was restricted by 80% in the diet of rats, the level of GSH in the blood actually increased due to adaptations in sulfur-amino acid metabolism
GSH↑, However, GSH concentrations were reduced in the liver
eff↑, Of note, methionine restriction is effective when the non-essential amino acid, cysteine, is absent from the diet or media.
polyA↓, MR may work by inhibiting prostate cancer cell proliferation, inhibiting the insulin/IGF-1 axis, or by reducing polyamine synthesis. MR-induced depletion of polyamines
TS↓, MR selectively reduces TS activity in prostate cancer cells by ~80% within 48 h, but does not affect TS activity in normal prostate epithelial cells
Raf↓, MR inhibits Raf and Akt oncogenic pathways, while increasing caspase-9 and the mitochondrial pro-apoptotic protein, Bak
Akt↓,
Casp9↑,
Bak↑,
P21↑, MR upregulating p21 and p27 (cell cycle inhibitors that halt cell cycle progression) in LNCaP cells
p27↑,
Insulin↓, MR-induced reduction in circulating insulin and IGF1, which have both been linked to tumor growth
IGF-1↓,

1613- EA,    Ellagitannins in Cancer Chemoprevention and Therapy
- Review, Var, NA
ROS↑, pomegranate ET inhibit pro-inflammatory pathways including, but not limited to, the NF-κB pathway, whose activation leads to immune reactions, inflammation, and the transcription of genes involved in cell survival, such as Bclx and inhibitors of apop
angioG↓, ET to inhibit angiogenesis
ChemoSen↑, ET could also be utilized to increase the sensitivity of tumor cells to standard chemotherapeutic drugs
BAX↑, induction of pro-apoptotic mediators (Bax and Bak), downregulation of Bcl-2 and Bcl-XL, and reduced expression of cyclin-dependent kinases 2, 4, 6, and cyclins D1, D2, and E
Bak↑,
Bcl-2↓,
Bcl-xL↓,
CDK2↓,
CDK4↓,
CDK6↓,
cycD1/CCND1↓,
cycE1↓,
TumCG↓, reduced LNCaP prostate cancer xenograft size, tumor vessel density, VEGF peptide levels and HIF-α expression after four weeks of treatment in severe combined immunodeficient mice
VEGF↓,
Hif1a↓,
eff↑, Oenothein B, a macrocyclic ET, and quercetin-3-O-glucuronide from Epilobium sp. herbs—used in traditional medicine to treat benign prostatic hyperplasia and prostatic adenoma—have been proven to strongly inhibit the proliferation of human prostate ca
COX2↓, pomegranate ET (i.e., punicalagin and ellagic acid) have been shown to suppress cyclooxygenase-2 (COX-2) protein expression in human colon cancer (HT-29) cells
TumCCA↑, pomegranate ET and their metabolites, i.e., urolithins A and C, inhibit HT-29 cells proliferation via G0/G1 and G2/M arrest
selectivity↑, interestingly, normal human breast epithelial cells (MCF-10A) were far less sensitive to the inhibitory effect of polyphenol-rich fractions.
Wnt/(β-catenin)↓, suppression of Wnt/β-catenin
*toxicity∅, LD50 of a standardized pomegranate fruit extract containing 30% punicalagin in Wistar rats was >5 g/kg b.w.,

3201- EGCG,    Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential
- Review, NA, NA
*AntiCan↑, EGCG’s therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes
*cardioP↑,
*neuroP↑,
*BioAv↝, Factors such as fasting, storage conditions, albumin levels, vitamin C, fish oil, and piperine have been shown to affect plasma concentrations and the overall bioavailability of EGCG
*BioAv↓, Conversely, bioavailability is reduced by processes such as air oxidation, sulfation, glucuronidation, gastrointestinal degradation, and interactions with Ca2+, Mg2+, and trace metals,
*BioAv↓, EGCG’s oral bioavailability is generally low, with marked differences observed across species, for example, bioavailability rates of 26.5% in CF-1 mice and just 1.6% in Sprague Dawley rats
*Dose↝, plasma concentrations exceeded 1 μM only when doses of 1 g or higher were administered.
*Half-Life↝, Specifically, a dose of 1600 mg yielded a Cmax of 3392 ng/mL (range: 130–3392 ng/mL), with peak levels observed between 1.3 and 2.2 h, AUC (0–∞) values ranging from 442 to 10,368 ng·h/mL, and a half-life (t1/2z) of 1.9 to 4.6 h.
*BioAv↑, Studies on the distribution of EGCG have revealed that, despite its limited absorption, it is rapidly disseminated throughout the body or quickly converted into metabolites
*BBB↑, Additionally, EGCG can cross the blood–brain barrier, allowing it to reach the brain
*hepatoP↓, Several studies have documented liver damage linked to green tea consumption [48,49,50,51,52,53].
*other↓, EGCG has also been shown to inhibit the intestinal absorption of non-heme iron in a dose-dependent manner in a controlled clinical trial
*Inflam↓, EGCG has been widely recognized for its anti-inflammatory effects
*NF-kB↓, EGCG has been shown to suppress NF-κB activation, inhibit its nuclear translocation, and block AP-1 activity
*AP-1↓,
*iNOS↓, downregulation of pro-inflammatory enzymes like iNOS and COX-2 and scavenging of ROS/RNS, including nitric oxide and peroxynitrite
*COX2↓,
*ROS↓,
*RNS↓,
*IL8↓, EGCG has been shown to suppress airway inflammation by reducing IL-8 release, a cytokine involved in neutrophil aggregation and ROS production.
*JAK↓, EGCG blocks the JAK1/2 signaling pathway
*PDGFR-BB↓, downregulate PDGFR and IGF-1R gene expression
*IGF-1R↓,
*MMP2↓, reduce MMP-2 mRNA expression
*P53↓, downregulation of the p53-p21 signaling pathway and the enhanced expression of Nrf2
*NRF2↑,
*TNF-α↓, 25 to 100 μM reduced the levels of TNF-α, IL-6, and ROS while enhancing the expression of E2F2 and superoxide dismutases (SOD1 and SOD2), enzymes vital for cellular antioxidant defense.
*IL6↓,
*E2Fs↑,
*SOD1↑,
*SOD2↑,
Casp3↑, EGCG has been shown to activate key apoptotic pathways, such as caspase-3 activation, cytochrome c release, and PARP cleavage, in various cell models, including PC12 cells exposed to oxidative stress
Cyt‑c↑,
PARP↑,
DNMTs↓, (1) the inhibition of DNA hypermethylation by blocking DNA methyltransferase (DNMT)
Telomerase↓, (2) the repression of telomerase activity;
Hif1a↓, (3) the suppression of angiogenesis via the inhibition of HIF-1α and NF-κB;
MMPs↓, (4) the prevention of cellular metastasis by inhibiting matrix metalloproteinases (MMPs);
BAX↑, (5) the promotion of apoptosis through the activation of pro-apoptotic proteins like BAX and BAK
Bak↑,
Bcl-2↓, while downregulating anti-apoptotic proteins like BCL-2 and BCL-XL;
Bcl-xL↓,
P53↑, (6) the upregulation of tumor suppressor genes such as p53 and PTEN;
PTEN↑,
TumCP↓, (7) the inhibition of inflammation and proliferation via NF-κB suppression;
MAPK↓, (8) anti-proliferative activity through the modulation of MAPK and IGF1R pathways
HGF/c-Met↓, EGCG inhibits hepatocyte growth factor (HGF), which is involved in tumor migration and invasion
TIMP1↑, EGCG has also been shown to influence the expression of tissue inhibitors of metalloproteinases (TIMPs) and MMPs, which are involved in tumorigenesis
HDAC↓, nhibition of UVB-induced DNA hypomethylation and modulation of DNMT and histone deacetylase (HDAC) activities
MMP9↓, inhibiting MMPs such as MMP-2 and MMP-9
uPA↓, EGCG may block urokinase-like plasminogen activator (uPA), a protease involved in cancer progression
GlutMet↓, EGCG can exert antitumor effects by inhibiting glycolytic enzymes, reducing glucose metabolism, and further suppressing cancer-cell growth
ChemoSen↑, EGCG’s combination with standard chemotherapy drugs may enhance their efficacy through additive or synergistic effects, while also mitigating chemotherapy-related side effects
chemoP↑,

3205- EGCG,    The Role of Epigallocatechin-3-Gallate in Autophagy and Endoplasmic Reticulum Stress (ERS)-Induced Apoptosis of Human Diseas
- Review, Var, NA - Review, AD, NA
Beclin-1↑, EGCG not only regulates autophagy via increasing Beclin-1 expression and reactive oxygen species generation,
ROS↑,
Apoptosis↑, Apoptosis is a common cell function in biology and is induced by endoplasmic reticulum stress (ERS)
ER Stress↑,
*Inflam↓, EGCG has health benefits including anti-tumor [15], anti-inflammatory [16], anti-diabetes [17], anti-myocardial infarction [18], anti-cardiac hypertrophy [19], anti-atherosclerosis [20], and antioxidant
*cardioP↑,
*antiOx↑,
*LDL↓, These effects are mainly related to (LDL) cholesterol inhibition, NF-κB inhibition, MPO activity inhibition, decreased levels of glucose and glycated hemoglobin in plasma, decreased inflammatory markers, and reduced ROS generation
*NF-kB↓,
*MPO↓,
*glucose↓,
*ROS↓,
ATG5↑, EGCG induced autophagy by enhancing Beclin-1, ATG5, and LC3B and promoted mitochondrial depolarization in breast cancer cells.
LC3B↑,
MMP↑,
lactateProd↓, 20 mg kg−1 EGCG significantly decreased glucose, lactic acid, and vascular endothelial growth factor (VEGF) levels
VEGF↓,
Zeb1↑, (20 uM) inhibited the proliferation through activating autophagy via upregulating ZEB1, WNT11, IGF1R, FAS, BAK, and BAD genes and inhibiting TP53, MYC, and CASP8 genes in SSC-4 human oral squamous cells [
Wnt↑,
IGF-1R↑,
Fas↑,
Bak↑,
BAD↑,
TP53↓,
Myc↓,
Casp8↓,
LC3II↑, increasing the LC3-II expression levels and induced apoptosis via inducing ROS in mesothelioma cell lines,
NOTCH3↓, but also could reduce partially Notch3/DLL3 to reduce drug-resistance and the stemness of tumor cells
eff↑, In combination therapies, low-intensity pulsed electric field (PEF) can improve EGCG to affect tumor cells; ultrasound (US) with tumor cells is the application of physical stimulation in cancer therapy.
p‑Akt↓, 20 μM EGCG increased intracellular ROS levels and LC3-II, and inhibited p-Akt in PANC-1 cells
PARP↑, 100 μM EGCG increased LC3-II, activated caspase-3 and PARP, and reduced p-Akt in HepG2
*Cyt‑c↓, EGCG protected neuronal cells against human viruses by inhibiting cytochrome c and Bax translocations, and reducing autophagy with increased LC3-II expression and decreased p62 expression
*BAX↓,
*memory↑, EGCG restored autophagy in the mTOR/p70S6K pathway to weaken memory and learning disorders induced by CUMS
*neuroP↑, Finally, EGCG increased the neurological scores through inhibiting cell death
*Ca+2?, EGCG treatment, [Ca2+]m and [Ca2+]i expressions were reduced and oxyhemoglobin-induced mitochondrial dysfunction lessened.
GRP78/BiP↑, MMe cells with EGCG treatment improved GRP78 expression in the endoplasmic reticulum, and induced EDEM, CHOP, XBP1, and ATF4 expressions, and increased the activity of caspase-3 and caspase-8.
CHOP↑, GRP78 accumulation converted UPR of MMe cells into pro-apoptotic ERS
ATF4↑,
Casp3↑,
Casp8↑,
UPR↑,

1516- EGCG,    Epigallocatechin Gallate (EGCG): Pharmacological Properties, Biological Activities and Therapeutic Potential
- Review, NA, NA
*Dose∅, A pharmacokinetic study in healthy individuals receiving single doses of EGCGrevealed that plasma concentrations exceeded 1 μM only with doses of >1 g
Half-Life∅, peak levels observed between 1.3 and 2.2 h (and a half-life (t1/2z) of 1.9 to 4.6 h)
BioAv∅, oral bioavailability of 20.3% relative to intravenous admistration
BBB↑, EGCG can cross the blood–brain barrier, allowing it to reach the brain
toxicity∅, Isbrucher et al. found no evidence of genotoxicity in rats following oral administration of EGCG at doses of 500, 1000, or 2000 mg/kg, or intravenous injections of 10, 25, or 50 mg/kg/day.
eff↓, interaction with the folate transporter has been reported, leading to reduced bioavailability of folic acid
Apoptosis↑,
Casp3↑,
Cyt‑c↑, cytochrome c release
cl‑PARP↑,
DNMTs↓,
Telomerase↓,
angioG↓,
Hif1a↓,
NF-kB↓,
MMPs↓,
BAX↑,
Bak↑,
Bcl-2↓,
Bcl-xL↓,
P53↑,
PTEN↑,
IGF-1↓,
H3↓,
HDAC1↓,
*LDH↓, reduces LDL cholesterol, decreases oxidative stress by neutralizing ROS
*ROS↓,

1155- F,    The anti-cancer effects of fucoidan: a review of both in vivo and in vitro investigations
- Review, NA, NA
*toxicity↓, Sprague–Dawley rats, researchers didn’t observe significant side effects when taking 0–1000 mg/kg fucoidan orally for 28 days.
Casp3↑,
Casp7↑,
Casp8↑,
Casp9↑,
VEGF↓,
angioG↓,
PI3K↓,
Akt↓,
PARP↑,
Bak↑,
BID↑,
Fas↑,
Mcl-1↓,
survivin↓,
XIAP↓,
ERK↓,
EMT↓, Fucoidan can reverse the EMT effectively
EM↑,
IM↓,
Snail↓,
Slug↓,
Twist↓,

2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
MMP↓, fraction of cells with reduced mitochondrial membrane potential also increased, indicating that fisetin-induced apoptosis also destroys mitochondria.
mtDam↑,
Cyt‑c↑, Cytochrome c and Smac/DIABLO levels are also released when the mitochondrial membrane potential changes, and this results in the activation of the caspase cascade and the cleavage of poly [ADP-ribose] polymerase (PARP)
Diablo↑,
Casp↑,
cl‑PARP↑,
Bak↑, Fisetin induced apoptosis in HCT-116 human colon cancer cells by upregulating proapoptotic proteins Bak and BIM and downregulating antiapoptotic proteins B cell lymphoma (BCL)-XL and -2.
BIM↑,
Bcl-xL↓,
Bcl-2↓,
P53↑, fisetin through the activation of p53
ROS↑, over generation of ROS, which is also directly initiated by fisetin, the stimulation of AMPK
AMPK↑,
Casp9↑, activating caspase-9 collectively, then activating caspase-3, leading to apopotosis
Casp3↑,
BID↑, Bid, AIF and the increase of the ratio of Bax to Bcl-2, causing the activation of caspase 3–9
AIF↑,
Akt↓, The inhibition of the Akt/mTOR/MAPK/
mTOR↓,
MAPK↓,
Wnt↓, Fisetin has been shown to degrade the Wnt/β/β-catenin signal
β-catenin/ZEB1↓,
TumCCA↑, fisetin triggered G1 phase arrest in LNCaP cells by activating WAF1/p21 and kip1/p27, followed by a reduction in cyclin D1, D2, and E as well as CDKs 2, 4, and 6
P21↑,
p27↑,
cycD1/CCND1↓,
cycE/CCNE↓,
CDK2↓,
CDK4↓,
CDK6↓,
TumMeta↓, reduces PC-3 cells' capacity for metastasis
uPA↓, fisetin decreased MMP-2 protein, messenger RNA (mRNA), and uPA levels through an ERK-dependent route
E-cadherin↑, Fisetin can upregulate the epithelial marker E-cadherin, downregulate the mesenchymal marker vimentin, and drastically lower the EMT regulator twist protein level at noncytotoxic dosages, studies have revealed.
Vim↓,
EMT↓,
Twist↓,
DNAdam↑, Fisetin induces apoptosis in the human nonsmall lung cancer cell line NCI-H460, which causes DNA breakage, the growth of sub-G1 cells, depolarization of the mitochondrial membrane, and activation of caspases 9, 3, which are involved in prod of iROS
ROS↓, fisetin therapy has been linked to a reduction in ROS, according to other research.
COX2↓, Fisetin lowered the expression of COX-1 protein, downregulated COX-2, and decreased PGE2 production
PGE2↓,
HSF1↓, Fisetin is a strong HSF1 inhibitor that blocks HSF1 from binding to the hsp70 gene promoter.
cFos↓, NF-κB, c-Fos, c-Jun, and AP-1 nuclear levels were also lowered by fisetin treatment
cJun↓,
AP-1↓,
Mcl-1↓, inhibition of Bcl-2 and Mcl-1 all contribute to an increase in apoptosis
NF-kB↓, Fisetin's ability to prevent NF-κB activation in LNCaP cells
IRE1↑, fisetin (20–80 µM) was accompanied by brief autophagy and the production of ER stress, which was shown by elevated levels of IRE1 α, XBP1s, ATF4, and GRP78 in A375 and 451Lu cells
ER Stress↑,
ATF4↑,
GRP78/BiP↑,
MMP2↓, lowering MMP-2 and MMP-9 proteins in melanoma cell xenografts
MMP9↓,
TCF-4↓, fisetin therapy reduced levels of β-catenin, TCF-4, cyclin D1, and MMP-7,
MMP7↓,
RadioS↑, fisetin treatment could radiosensitize human colorectal cancer cells that are resistant to radiotherapy.
TOP1↓, fisetin blocks DNA topoisomerases I and II in leukemia cells.
TOP2↓,

5052- HPT,    Hyperthermia Induces Apoptosis through Endoplasmic Reticulum and Reactive Oxygen Species in Human Osteosarcoma Cells
- in-vitro, OS, U2OS
Apoptosis↑, Treatment at 43 °C for 60 min induced apoptosis in human OS cell lines, but not in primary bone cells.
ROS↑, hyperthermia was associated with increases of intracellular reactive oxygen species (ROS) and caspase-3 activation in U-2 OS cells.
Casp3↑,
mtDam↑, Mitochondrial dysfunction was followed by the release of cytochrome c from the mitochondria, and was accompanied by decreased anti-apoptotic Bcl-2 and Bcl-xL, and increased pro-apoptotic proteins Bak and Bax.
Cyt‑c↑,
Bcl-2↓,
Bcl-xL↓,
Bak↑,
BAX↓,
ER Stress↑, Hyperthermia triggered endoplasmic reticulum (ER) stress, which was characterized by changes in cytosolic calcium levels, as well as increased calpain expression and activity.
Ca+2↝,
cal2↑,

2259- MFrot,  MF,    Method and apparatus for oncomagnetic treatment
- in-vitro, GBM, NA
MMP↓, Oncomagnetic patent Fig 2
Bcl-2↓,
BAX↑,
Bak↑,
Cyt‑c↑,
Casp3↑, caspase staining rises progressively until after 30 min most of the cells fluoresce positive for caspase, revealing activation of this enzyme
Casp9↑,
DNAdam↑,
ROS↑, applying the oscillating magnetic field to the tissue increases the production of reactive oxygen species (ROS )
lactateProd↑,
Apoptosis↑,
MPT↑, opening of the mitochondrial membrane permeability transition pore
*selectivity↑, repetitive magnetic stimulation has shown decreased apoptosis in non -cancerous cells .
eff↑, oncomagnetic therapy may be performed in conjunction with other forms of therapy such as with chemotherapy, other forms of radiative therapy, with drugs and prescriptions, etc
MMP↓, OMF which in turn produces rapidly fluctuating or sustained depolarizations of the mitochondrial membrane potential (MMP) in the tissue .
selectivity↑, Because normal cells have a larger amount of mitochondria, have lower demand for ATP, and are not under stress, disruption of electron flow and small amount of ROS formation and MMP depolarization does not trigger apoptosis
TCA?, decrease in Krebs cycle metabolites
H2O2↑, increase in peroxide levels in GBM cells following stimulation by the system 100 using a rotating magnet
eff↑, combine the administration of BHB , or acetoacetate , or free fatty acid, or branched chain amino acid, or cryptochrome agonist , or MGMT inhibitor, or DNA alkylating agent, or DNA methylating agent, and OMF as a more effective treatment of cancer
*antiOx↑, upregulation of antioxidant mechanisms due to the application of OMFs further protects non -cancerous cells from any ROS -mediated apoptosis
H2O2↑, The experiments showed rapid increases in the levels of superoxide and H2O2 in GBM cells
eff↓, To test whether cell death is caused by the OMF - induced increase in ROS , a potent antioxidant Trolox was used to counteract it, while measuring the decrease in GBM cell count due to 4 h exposure to OMF.
GSH/GSSG↓, GSH/GSSG ratio almost exactly half that seen in control cells
*toxicity∅, No Cytotoxic Effect in Normal Cells
OS↑, OMF -Induced Prolongation of Survival in a Mouse Xenograft Model of GBM

1799- NarG,    Naringenin as potent anticancer phytocompound in breast carcinoma: from mechanistic approach to nanoformulations based therapeutics
- Review, NA, NA
TumCCA↑, inhibition of the cell cycle
BioAv↑, oral bioavailability was determined to be 5.81%.Novel delivery strategies such as nanoparticles, liposomes, and micelles have been investigated to improve their bioavailability
Half-Life∅, researchers recorded a maximum concentration (Cmax) of 2009.51 ng/mL in 3.67 h after administration. elimination half-life was found to be 2.31 h.
TNF-α↓,
Casp8↑,
BAX↑,
Bak↑,
EGF↓,
mTOR↓,
PI3K↓,
ERK↓,
Akt↓,
NF-kB↓,
VEGF↓,
angioG↓,
antiOx↑,
EMT↓, Naringenin reduces the metastatic efficacy of breast cancer cells by EMT suppression
OS↑, Oral administration of naringenin dramatically reduced the number of metastatic tumor cells in the lungs and prolonged the lifespan of mice that had their tumors removed
MAPK↓, Naringenin inhibited the MAPK and PI3K pathways
ChemoSen↑, In MCF-7 breast cancer cells, combination therapy using NGE and tamoxifen was more effective than either drug alone
MMP9↓, downregulating the expression of MMP-9 and MMP-2
MMP2↓,
ROS↑, combination treatment increases ROS generation
ROS↑, demonstrated the antitumor effects of naringenin nanoparticles through increased ROS levels, GSH attenuation, and caspase-3 activation, which ultimately induced apoptosis
GSH↓,
Casp3↑,
ROS↑, This review concludes that naringenin can reduce carcinogenesis through pleiotropic processes such as antioxidative, apoptotic-inducing ROS generation, and cell cycle arrest

4643- OLE,  HT,    Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine
- Review, Var, NA
TumCCA↑, A similar S phase cell cycle arrest was also observed for 800 μM HT, and induction of apoptosis also took place after 24 h incubation of HT-29 cells with 600 μM and 800 μM HT
Apoptosis↑,
ER Stress↑, 400 μM HT triggered endoplasmic reticulum stress in HT-29 cells, with activation of unfolded protein response,
UPR↑,
CHOP↑, increase in CHOP protein levels (responsible for ROS production and Bcl-2 downregulation) and NADPH oxidase 4 (NOX4)
ROS↑,
Bcl-2↓,
NOX4↑,
Hif1a↓, Moreover, 400 μM HT reduced HIF-1α protein levels
MMP2↓, figure 2
MMP↓,
VEGF↓,
Akt↓,
NF-kB↓,
p65↓,
SIRT3↓,
mTOR↓,
Catalase↓,
SOD2↓,
FASN↓,
STAT3↓,
HDAC2↓,
HDAC3↓,
BAD↑, figure 2 upregulated
BAX↑,
Bak↑,
Casp3↑,
Casp9↑,
PARP↑,
P53↑,
P21↑,
p27↑,
Half-Life↝, HT added to extra virgin olive oil produced a plasma peak of 3.79 ng/mL after 30 min, followed by a rapid decline in HT plasma concentration
BioAv↓, On the basis of these pieces of data, it becomes evident that cytotoxicity and anti-cancer effects of OLE and HT were recorded at concentrations largely exceeding those reachable with diet/olive oil consumption
BioAv↓, Thus, it is difficult to imagine how OLE and HT may be used as cancer-preventive/treating agents if the route of administration is ingestion.
selectivity↑, However, even at high concentrations, OLE and HT seem to be selectively cytotoxic for cancer cells, with no or negligible/minimal effects on non-cancer cells,
RadioS↑, 200 μM OLE enhanced cell radiosensitivity in vitro and in vivo after injection in BALB/C nude mice
*ROS↓, A lot of experimental data in vivo and in vitro have definitively demonstrated the ROS scavenger ability of OLE and HT, which can also act on antioxidant cellular mechanisms restoring ROS homeostasis,
*GSH↑, including promotion of the increase in reduced glutathione levels (GSH), depletion of lipid peroxidation product malondialdehyde (MDA), intensification of the expression and/or activity of detoxicating enzymes SOD, CAT, glutathione-S-transferase (GST
*MDA↓,
*SOD↑,
*Catalase↑,
*NRF2↑, and nuclear factor E2-related factor 2 (Nrf2) upregulation/transactivation,
*chemoP↑, OLE and HT have shown an important ability to mitigate the toxicity elicited by chemotherapeutic agents mainly through their largely demonstrated antioxidant and ROS scavenger activity.
*Inflam↓, OLE and HT exhibit an anti-inflammatory activity that has been demonstrated in multiple in vivo and in vitro models,
PPARγ↑, HT-dependent anti-inflammatory effect was also mediated by HT-elicited increase in protein levels of PPARγ

3369- QC,    Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects
- Review, Pca, NA
FAK↓, Quercetin can inhibit HGF-induced melanoma cell migration by inhibiting the activation of c-Met and its downstream Gabl, FAK and PAK [84]
TumCCA↑, stimulation of cell cycle arrest at the G1 stage
p‑pRB↓, mediated through regulation of p21 CDK inhibitor and suppression of pRb phosphorylation resulting in E2F1 sequestering.
CDK2↑, low dose of quercetin has brought minor DNA injury and Chk2 induction
CycB/CCNB1↓, quercetin has a role in the reduction of cyclin B1 and CDK1 levels,
CDK1↓,
EMT↓, quercetin suppresses epithelial to mesenchymal transition (EMT) and cell proliferation through modulation of Sonic Hedgehog signaling pathway
PI3K↓, quercetin on other pathways such as PI3K, MAPK and WNT pathways have also been validated in cervical cancer
MAPK↓,
Wnt↓,
ROS↑, colorectal cancer, quercetin has been shown to suppress carcinogenesis through various mechanisms including affecting cell proliferation, production of reactive oxygen species and expression of miR-21
miR-21↑,
Akt↓, Figure 1 anti-cancer mechanisms
NF-kB↓,
FasL↑,
Bak↑,
BAX↑,
Bcl-2↓,
Casp3↓,
Casp9↑,
P53↑,
p38↑,
MAPK↑,
Cyt‑c↑,
PARP↓,
CHOP↑,
ROS↓,
LDH↑,
GRP78/BiP↑,
ERK↑,
MDA↓,
SOD↑,
GSH↑,
NRF2↑,
VEGF↓,
PDGF↓,
EGF↓,
FGF↓,
TNF-α↓,
TGF-β↓,
VEGFR2↓,
EGFR↓,
FGFR1↓,
mTOR↓,
cMyc↓,
MMPs↓,
LC3B-II↑,
Beclin-1↑,
IL1β↓,
CRP↓,
IL10↓,
COX2↓,
IL6↓,
TLR4↓,
Shh↓,
HER2/EBBR2↓,
NOTCH↓,
DR5↑, quercetin has enhanced DR5 expression in prostate cancer cells
HSP70/HSPA5↓, Quercetin has also suppressed the upsurge of hsp70 expression in prostate cancer cells following heat treatment and enhanced the quantity of subG1 cells
CSCs↓, Quercetin could also suppress cancer stem cell attributes and metastatic aptitude of isolated prostate cancer cells through modulating JNK signaling pathway
angioG↓, Quercetin inhibits angiogenesis-mediated of human prostate cancer cells through negatively modulating angiogenic factors (TGF-β, VEGF, PDGF, EGF, bFGF, Ang-1, Ang-2, MMP-2, and MMP-9)
MMP2↓,
MMP9↓,
IGFBP3↑, Quercetin via increasing the level of IGFBP-3 could induce apoptosis in PC-3 cells
uPA↓, Quercetin through decreasing uPA and uPAR expression and suppressing cell survival protein and Ras/Raf signaling molecules could decrease prostate cancer progression
uPAR↓,
RAS↓,
Raf↓,
TSP-1↑, Quercetin through TSP-1 enhancement could effectively inhibit angiogenesis

1469- SFN,    Sulforaphane enhances the therapeutic potential of TRAIL in prostate cancer orthotopic model through regulation of apoptosis, metastasis, and angiogenesis
- in-vitro, Pca, PC3 - in-vitro, Pca, LNCaP - in-vivo, Pca, NA
eff↑, Sulforaphane enhanced the therapeutic potential of TRAIL in PC-3 cells and sensitized TRAIL-resistant LNCaP cells.
ROS↑,
MMP↓,
Casp3↑,
Casp9↑,
DR4↑,
DR5↑,
BAX↑,
Bak↑,
BIM↑,
NOXA↑,
Bcl-2↓,
Bcl-xL↓,
Mcl-1↓,
eff↓, quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against sulforaphane-induced ROS generation, mitochondrial membrane potential disruption, caspase-3 activation, and apoptosis.
TumCG↓,
TumCP↓,
eff↑, enhanced the antitumor activity of TRAIL.
NF-kB↓,
PI3K↓,
Akt↓,
MEK↓,
ERK↓,
angioG↓, combination of sulforaphane and TRAIL was more effective in inhibiting markers of angiogenesis and metastasis and activating FOXO3a transcription factor than single agent alone.
FOXO3↑,

5332- TFdiG,    Theaflavin-3,3′-digallate triggers apoptosis in osteosarcoma cells via the caspase pathway
- vitro+vivo, OS, 143B - in-vitro, OS, U2OS
tumCV↓, TF3 significantly reduced the viability of 143B and U2OS cells.
cl‑Casp3↑, TF3 upregulated the expression of cleaved caspase-3 and cleaved caspase-9 in osteosarcoma cells.
cl‑Casp9↑,
p‑γH2AX↑, TF3 increased the levels of phosphorylated histone H2Ax, Bax, Bak1, and cytochrome c, while reducing the levels of Mcl-1 and survivin in osteosarcoma cells.
BAX↑,
Bak↑,
Cyt‑c↑,
Mcl-1↓,
survivin↓,
TumVol↓, TF3 significantly reduced the average tumor volume in the xenograft model.
Wnt↓, TF3 also inhibited the proliferation of ovarian cancer stem cells by suppressing the Wnt/β-Catenin pathway 14.
β-catenin/ZEB1↓,
Dose↝, mice were fed TF3 at experimental concentrations (10 and 20 mg/kg) thrice a week.
ROS↑, TF3 treatment significantly elevated ROS levels in 143B and U2OS cells. Specifically, ROS levels were significantly higher in cells treated with 75 or 100 μM TF3 than in control cells.
eff↓, Moreover, treatment with NAC, an antioxidant, significantly reversed cell viability after TF3 treatment
TumW↓, In the xenograft mouse model, TF3 treatment reduced tumor volume, tumor weight, and Ki-67 expression.
Ki-67↓,

3423- TQ,    Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics
- Review, Var, NA
AntiCan↑, Thymoquinone is a natural product with anticancer activity.
Inflam↓, Thymoquinone has been shown to exert anti-inflammatory, antidiabetic, antihypertensive, antimicrobial, analgesic, immunomodulatory, spasmolytic, hepatoprotective, renal-protective, gastroprotective, bronchodilatory, antioxidant and antineoplastic eff
hepatoP↑,
RenoP↑,
BAX↑, Thymoquinone can upregulate proapoptotic genes and proteins, such as Bax/Bak, or downregulate antiapoptotic genes and proteins, such as Bcl-2, Bcl-xL, among others, as well as modulating the caspase pathway
Bak↑,
Bcl-2↓,
Bcl-xL↓,
ROS↑, through the generation of reactive oxygen species (ROS)
P53↑, overexpressed or activated by thymoquinone; for example, p53, PTEN, p21, p27 and breast cancer type 1 susceptibility protein (BRCA1), among others,
PTEN↑,
P21↑,
p27↑,
BRCA1↑,
PI3K↓, (PI3K)/Akt and mitogen-activated protein kinase (MAPK)/ERK, have been found to be inhibited by thymoquinone
Akt↓,
MAPK↓,
ERK↓,
p‑ERK↓, thymoquinone reduces ERK phosphorylation and matrix metalloproteinase (MMP) secretion by downregulating focal adhesion kinase (FAK)
MMPs↓,
FAK↓,
Twist↓, downregulates Twist1 and Zeb1 transcription factors, and thus inhibits epithelial to mesenchymal transition (EMT) and subsequently inhibits cancer metastasis
Zeb1↓,
EMT↓,
TumMeta↓,
angioG↓, thymoquinone can inhibit angiogenesis by interfering with essential steps of neovascularization, such as suppressing proangiogenic vascular endothelial growth factor (VEGF)
VEGF↓,
HDAC↓, HDACs are usually overexpressed in MCF-7 breast cancer cells, and thymoquinone can act as a HDAC inhibitor (HDACi) that potently induces apoptosis through inducing acetylation of histones and inhibiting deacetylation of histones.
Maspin↑, thymoquinone reactivates HDAC target genes (p21 and Maspin), inducing the upregulation of Bax
SIRT1↑, thymoquinone can upregulate SIRT1 expression in neonatal rat cardiomyocytes and consequently deacetylates p53; thus, it can act as an apoptosis inducer
DNMT1↓, Collectively, they suggested that thymoquinone induces methylation of DNA via binding with DNMT1 and suppressing its expression,
DNMT3A↓, thymoquinone decreases the expression of some important epigenetic proteins like DNMT1,3A,3B, G9A, HDAC1,4,9, KDM1B, KMT2A,B,C,D,E and UHRF1 in Jurkat cells,
HDAC1↓,
HDAC4↓,


Showing Research Papers: 1 to 27 of 27

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 27

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 1,   Catalase↓, 1,   ENOX2↓, 1,   GSH↓, 1,   GSH↑, 2,   GSH/GSSG↓, 1,   H2O2↑, 2,   ICD↑, 1,   MDA↓, 1,   NOX4↑, 1,   NRF2↑, 1,   OXPHOS↓, 1,   PAO↑, 1,   RNS↑, 1,   ROS↓, 2,   ROS↑, 23,   mt-ROS↑, 1,   SIRT3↓, 1,   SOD↑, 1,   SOD2↓, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   ATP∅, 1,   compIII↑, 1,   EGF↓, 2,   FGFR1↓, 1,   Insulin↓, 2,   MEK↓, 1,   mitResp↓, 1,   MMP↓, 10,   MMP↑, 1,   MPT↑, 1,   mtDam↑, 2,   p‑p42↓, 1,   Raf↓, 3,   XIAP↓, 4,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 3,   cMyc↓, 2,   cMyc↑, 1,   FASN↓, 1,   GlutMet↓, 1,   lactateProd↓, 1,   lactateProd↑, 1,   LDH↓, 1,   LDH↑, 1,   polyA↓, 1,   PPARγ↑, 1,   SIRT1↓, 2,   SIRT1↑, 1,   SSAT↑, 1,   TCA?, 1,   TS↓, 1,  

Cell Death ⓘ

Akt↓, 8,   p‑Akt↓, 4,   Apoptosis↑, 12,   BAD↑, 4,   Bak↑, 27,   BAX↓, 1,   BAX↑, 20,   Bcl-2↓, 18,   Bcl-xL↓, 9,   BID↑, 2,   BIM↑, 4,   Casp↑, 3,   Casp3↓, 1,   Casp3↑, 17,   cl‑Casp3↑, 2,   Casp7↑, 1,   Casp8↓, 1,   Casp8↑, 3,   Casp9↑, 10,   cl‑Casp9↑, 2,   Cyt‑c↑, 11,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 2,   Fas↑, 2,   FasL↑, 1,   HGF/c-Met↓, 1,   MAPK↓, 5,   MAPK↑, 2,   Mcl-1↓, 5,   Myc↓, 1,   NOXA↑, 2,   p27↑, 4,   p38↑, 2,   PUMA↑, 1,   survivin↓, 4,   Telomerase↓, 2,   TRAIL↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   H3↓, 1,   miR-21↑, 1,   other↓, 1,   p‑pRB↓, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 5,   p‑eIF2α↑, 1,   ER Stress↑, 7,   GRP78/BiP↑, 3,   HSF1↓, 1,   HSP70/HSPA5↓, 1,   HSP90↓, 1,   IRE1↑, 1,   UPR↑, 2,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 2,   LC3B↑, 1,   LC3B-II↑, 1,   LC3II↑, 1,  

DNA Damage & Repair ⓘ

BRCA1↑, 1,   DNAdam↑, 3,   DNMT1↓, 1,   DNMT3A↓, 1,   DNMTs↓, 3,   P53↓, 1,   P53↑, 9,   ac‑P53↑, 1,   PARP↓, 1,   PARP↑, 4,   cl‑PARP↑, 6,   PCNA↓, 1,   RAD51↓, 1,   TP53↓, 1,   γH2AX↑, 1,   p‑γH2AX↑, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 2,   CDK2↑, 1,   CDK4↓, 2,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   cycE1↓, 1,   P21↑, 7,   p‑RB1↓, 1,   TumCCA↑, 10,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   CSCs↓, 2,   EMT↓, 6,   EMT↑, 1,   ERK↓, 5,   ERK↑, 1,   p‑ERK↓, 1,   FGF↓, 1,   FOXO3↑, 1,   HDAC↓, 3,   HDAC1↓, 2,   HDAC2↓, 1,   HDAC3↓, 1,   HDAC4↓, 1,   HDAC8↓, 1,   IGF-1↓, 2,   IGF-1R↑, 1,   IGFBP3↑, 1,   mTOR↓, 5,   NOTCH↓, 1,   NOTCH1↓, 1,   NOTCH3↓, 1,   PI3K↓, 5,   PI3K↑, 1,   PIAS-3↑, 1,   PTEN↑, 3,   RAS↓, 2,   Shh↓, 1,   Src↓, 1,   p‑STAT1↓, 1,   STAT3↓, 3,   STAT3↑, 1,   TCF-4↓, 1,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 3,   Wnt↓, 4,   Wnt↑, 1,   Wnt/(β-catenin)↓, 1,  

Migration ⓘ

AP-1↓, 2,   Ca+2↑, 1,   Ca+2↝, 1,   cal2↑, 1,   E-cadherin↑, 3,   EM↑, 1,   FAK↓, 3,   p‑FAK↓, 1,   Ki-67↓, 1,   MMP2↓, 4,   MMP7↓, 1,   MMP9↓, 4,   MMPs↓, 5,   N-cadherin↓, 2,   p‑p44↓, 1,   p‑pax↓, 1,   PDGF↓, 1,   Slug↓, 1,   Snail↓, 2,   TGF-β↓, 2,   TIMP1↑, 2,   TSP-1↑, 1,   TumCI↓, 1,   TumCMig↓, 3,   TumCP↓, 6,   TumCP↑, 1,   TumMeta↓, 2,   TumMeta↑, 1,   Twist↓, 3,   uPA↓, 3,   uPAR↓, 1,   Vim↓, 3,   Zeb1↓, 1,   Zeb1↑, 1,   β-catenin/ZEB1↓, 4,  

Angiogenesis & Vasculature ⓘ

angioG↓, 10,   ATF4↑, 3,   EGFR↓, 1,   Hif1a↓, 5,   VEGF↓, 8,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   CRP↓, 1,   IL10↓, 1,   IL1β↓, 1,   IL6↓, 1,   Inflam↓, 3,   NF-kB↓, 10,   p65↓, 1,   PD-L1↑, 1,   PGE2↓, 1,   SOCS-3↑, 1,   SOCS1↑, 1,   TLR4↓, 1,   TNF-α↓, 3,  

Cellular Microenvironment ⓘ

IM↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 4,   BioAv↑, 1,   BioAv∅, 1,   ChemoSen↓, 1,   ChemoSen↑, 4,   Dose↝, 2,   Dose∅, 2,   eff↓, 5,   eff↑, 12,   Half-Life↓, 1,   Half-Life↝, 2,   Half-Life∅, 2,   RadioS↑, 3,   selectivity↑, 5,  

Clinical Biomarkers ⓘ

BRCA1↑, 1,   CRP↓, 1,   E6↓, 1,   E7↓, 1,   EGFR↓, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,   Ki-67↓, 1,   LDH↓, 1,   LDH↑, 1,   Maspin↑, 1,   Myc↓, 1,   PD-L1↑, 1,   TP53↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 3,   chemoP↑, 1,   chemoPv↑, 1,   hepatoP↑, 1,   OS↑, 2,   RenoP↑, 1,   toxicity∅, 1,   TumVol↓, 1,   TumW↓, 1,  
Total Targets: 272

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 5,   Catalase↑, 1,   GSH↑, 2,   MDA↓, 1,   MPO↓, 1,   NRF2↑, 2,   RNS↓, 1,   ROS↓, 6,   ROS∅, 1,   SOD↑, 1,   SOD1↑, 1,   SOD2↑, 1,  

Mitochondria & Bioenergetics ⓘ

Insulin↑, 1,  

Core Metabolism/Glycolysis ⓘ

glucose↓, 2,   GlucoseCon↑, 1,   LDH↓, 1,   LDL↓, 1,  

Cell Death ⓘ

BAX↓, 1,   Cyt‑c↓, 1,   iNOS↓, 1,   TRPV1↑, 1,  

Transcription & Epigenetics ⓘ

other↓, 1,  

DNA Damage & Repair ⓘ

P53↓, 1,  

Cell Cycle & Senescence ⓘ

E2Fs↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

IGF-1R↓, 1,  

Migration ⓘ

AntiAg↑, 1,   AP-1↓, 1,   Ca+2?, 1,   MMP2↓, 1,  

Angiogenesis & Vasculature ⓘ

PDGFR-BB↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↓, 3,   Inflam↑, 1,   JAK↓, 1,   NF-kB↓, 2,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 1,   BioAv↝, 1,   Dose↝, 1,   Dose∅, 1,   Half-Life↝, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

BP↓, 1,   IL6↓, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   cardioP↑, 2,   chemoP↑, 1,   hepatoP↓, 1,   hepatoP↑, 1,   memory↑, 1,   neuroP↑, 2,   Pain↓, 1,   toxicity↓, 1,   toxicity∅, 2,  
Total Targets: 59

Scientific Paper Hit Count for: Bak, BAK or BAK1
3 Ashwagandha(Withaferin A)
3 EGCG (Epigallocatechin Gallate)
2 Silver-NanoParticles
2 Capsaicin
2 Curcumin
1 Gemcitabine (Gemzar)
1 Apigenin (mainly Parsley)
1 immunotherapy
1 Berberine
1 Chrysin
1 diet Methionine-Restricted Diet
1 Ellagic acid
1 Fucoidan
1 Fisetin
1 Hyperthermia
1 Magnetic Field Rotating
1 Magnetic Fields
1 Naringin
1 Oleuropein
1 HydroxyTyrosol
1 Quercetin
1 Sulforaphane (mainly Broccoli)
1 Aflavin-3,3′-digallate
1 Thymoquinone
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#:632  State#:%  Dir#:2
  wNotes=on  sortOrder:rid,rpid

 

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