NRF2 Cancer Research Results

NRF2, nuclear factor erythroid 2-related factor 2: Click to Expand ⟱
Source: TCGA
Type: Antiapoptotic
Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. Thought of as "Master Regulator" of antioxidant response.
-One way to estimate Nrf2 induction is through the expression of NQO1.
NQO1, the most potent inducer:
SFN 0.2 μM,
quercetin (2.5 μM),
curcumin (2.7 μM),
Silymarin (3.6 μM),
tamoxifen (5.9 μM),
genistein (6.2 μM ),
beta-carotene (7.2μM),
lutein (17 μM),
resveratrol (21 μM),
indol-3-carbinol (50 μM),
chlorophyll (250 μM),
alpha-cryptoxanthin (1.8 mM),
and zeaxanthin (2.2 mM)

1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects.
2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death.
3. However there are some cases where increasing Nrf2 paradoxically causes an increase in ROS (cancer cells). Such as cases of Mitochondial overload, signal crosstalk, reductive stress

-In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies.
-Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate.
Decreased Nrf2 expression: Skine, Liver, Pancreatic.
-Nrf2 is a cytoprotective transcription factor which demonstrated both a negative effect as well as a positive effect on cancer
- "promotes Nrf2 translocation from the cytoplasm to the nucleus," means facilitates the movement of Nrf2 into the nucleus, thereby enhancing the cell's antioxidant and cytoprotective responses. -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1.

Nrf2 Inhibitors and Activators
Nrf2 Inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin
Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api
- potent Nrf2 inducers from plants include sulforaphane, curcumin, EGCG, resveratrol, caffeic acid phenethyl ester, wasabi, cafestol and kahweol (coffee), cinnamon, ginger, garlic, lycopene, rosemany

Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue.
– In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis.
– In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity.
– This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming.
– Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies.
– High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types.
– While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression.

NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS).
-Brusatol: most cited natural inhibitors of Nrf2.
-Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent.
-Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: Dose and context dependent .
-Oridonin:
-Wogonin: although its effects might be cell‑ and dose‑specific.
- Withaferin A

Scientific Papers found: Click to Expand⟱
4428- AgNPs,    p38 MAPK Activation, DNA Damage, Cell Cycle Arrest and Apoptosis As Mechanisms of Toxicity of Silver Nanoparticles in Jurkat T Cells
- in-vitro, AML, Jurkat
toxicity↝, The effect of Ag ions was also investigated and compared with that of AgNPs, as it is anticipated that Ag ions will be released from AgNPs, which may be responsible for their toxicity.
tumCV↓, Cell viability tests indicated high sensitivity of Jurkat T cells when exposed to AgNPs compared to Ag ions
ROS↑, AgNPs and Ag ions induce similar levels of cellular reactive oxygen species during the initial exposure period and; after 24 h, they were increased on exposure to AgNPs compared to Ag ions, which suggest that oxidative stress may be an indirect caus
p38↑, AgNPs exposure activates p38 mitogen-activated protein kinase through nuclear factor-E2-related factor-2 and nuclear factor-kappaB signaling pathways, subsequently inducing DNA damage, cell cycle arrest and apoptosis.
NRF2↓,
NF-kB↝,
DNAdam↑,
Apoptosis↑,

365- AgNPs,    Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species
- in-vitro, Hepat, HepG2
ROS↑,
GlucoseCon↓,
TumCD↑,
NRF2↓, Decreased mRNA levels of Nrf2

256- AL,  doxoR,    Allicin Overcomes Doxorubicin Resistance of Breast Cancer Cells by Targeting the Nrf2 Pathway
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
NRF2↓,
HO-1↓,
p‑Akt↓,

265- ALA,    Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies
- in-vitro, Pca, LNCaP - in-vitro, Pca, DU145
ROS↓, ALA decreased ROS production, SOD1 and GSTP1 protein expression
SOD↓, SOD1, DU145
GSTP1/GSTπ↓,
NRF2↓, significantly reduced the cytosolic and nuclear content of the transcription factor Nrf2
p62↓, du145
p62↑, LNCaP
SOD↑, LNCaP
p‑mTOR↑, revealed that in both cancer cells, ALA, by upregulating pmTOR expression, reduced the protein content of two autophagy initiation markers, Beclin-1 and MAPLC3.
Beclin-1↓,
ROS↑, Interestingly, in LNCaP cells, we observed an almost significant increase in ROS content (p = 0.06) after ALA compared to the control, concomitantly with a significant upregulation of the antioxidant enzyme SOD1 after 48 h.
SOD1↑,

267- ALA,    α-Lipoic Acid Targeting PDK1/NRF2 Axis Contributes to the Apoptosis Effect of Lung Cancer Cells
- vitro+vivo, Lung, A549 - vitro+vivo, Lung, PC9
Apoptosis↑,
ROS↑, mitochondrial ROS(remarkably increased)
PDK1↓,
NRF2↓,
PDK1↓,
Bcl-2↓,
Casp9↑,
Dose∅, 1.5 mM LA for 24 h

1547- Api,    Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading
- Review, NA, 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↓,

2639- Api,    Plant flavone apigenin: An emerging anticancer agent
- Review, Var, NA
*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).

2593- Api,    Apigenin promotes apoptosis of 4T1 cells through PI3K/AKT/Nrf2 pathway and improves tumor immune microenvironment in vivo
- in-vivo, BC, 4T1
TumCP↓, API suppresses 4T1 cells proliferation
TumCMig↓, API restraints 4T1 cells migration and invasion
TumCI↓,
Apoptosis↑, API triggers 4T1 apoptosis and modulates the expression levels of apoptotic-associated proteins in 4T1 cells
MMP↑, API triggers the depolarization of ΔΨm in 4T1 cells
ROS↑, API induces ROS generation
p‑PI3K↓, The results revealed a significant downregulation of p-PI3K/PI3K, p-AKT/AKT, and Nrf2 in 4T1 cells following API treatment
PI3K↓,
Akt↓,
NRF2↓,
AntiTum↑, API exhibits anti-tumor activity in mice
OS↑, results of animal survival experiments show that API can appropriately prolong the survival of mice with mammary gland tumors

2594- Api,  docx,    Targeted hyaluronic acid-based lipid nanoparticle for apigenin delivery to induce Nrf2-dependent apoptosis in lung cancer cells
- in-vitro, Lung, A549
NRF2↓, Apigenin (4,5,7-trihydroxyflavone; APG), as a typically dietary flavonoid, is a potent small molecule inhibitor of Nrf2 that has been studied for its Nrf2 and anticancer activity in different cancers
ChemoSen↑, overcome limitations of the clinical use of APG and improve the efficacy of DTX in lung cancer.

2596- Api,  LT,    Natural Nrf2 Inhibitors: A Review of Their Potential for Cancer Treatment
- Review, Var, NA
NRF2↓, In addition, natural compounds such as apigenin, luteolin, chrysin and brusatol have been shown to be potent Nrf2 inhibitors.
chemoPv↑, These findings suggest that natural Nrf2 inhibitors could be utilized as chemopreventive and chemotherapeutic agents, as well as tumor sensitizers for conventional radiotherapy and chemotherapy.
ChemoSen↑,

2586- Api,  doxoR,    Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway
- in-vitro, HCC, Bel-7402
NRF2↓, APG dramatically reduced Nrf2 expression at both the messenger RNA and protein levels through downregulation of PI3K/Akt pathway, leading to a reduction of Nrf2-downstream genes.
ChemoSen↑, APG can be used as an effective adjuvant sensitizer to prevent chemoresistance by downregulating Nrf2 signaling pathway.

4993- ART/DHA,    Dihydroartemisinin inhibits galectin-1–induced ferroptosis resistance and peritoneal metastasis of gastric cancer via the Nrf2–HO-1 pathway
- vitro+vivo, GC, NA
Ferroptosis↑, DHA suppresses galectin-1-promoted GCPM via the PI3K/Akt/Nrf2/HO-1 pathway in vitro
NRF2↓, DHA promotes ferroptosis by downregulating Nrf2/HO-1
HO-1↓,
PI3K↓, We found that DHA significantly affected galectin-1 expression and inhibited PI3K/Akt activation
Akt↓,
TumMeta↓, DHA inhibits peritoneal metastasis through the PI3K/Akt/Nrf2/HO-1 pathway in vivo

1076- ART/DHA,    The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer
- Review, NA, NA
Ferroptosis↑,
ROS↑, interaction between heme-derived iron and ART will result in the production of ROS
ER Stress↑,
i-Iron↓, DHA can cause intracellular iron depletion in a time- and dose-dependent manner
TumAuto↑,
AMPK↑,
mTOR↑,
P70S6K↑,
Fenton↑,
lipid-P↑,
ROS↑,
ChemoSen↑, combination of ART and Nrf2 inhibitors to promote ferroptosis may have more efficient anticancer effects without damaging normal cells.
NRF2↑, Liu et al. discovered that ART covalently targets Keap1 at Cys151 to activate the Nrf2-dependent pathway [94
NRF2↓, inhibition of Nrf2-related gene expression accelerated erastin and sorafenib-induced ferroptosis [45]. More importantly, an accumulating body of research suggests that ART may induce ferroptosis in cancer cells by regulating the above molecules.

3172- Ash,    Implications of Withaferin A for the metastatic potential and drug resistance in hepatocellular carcinoma cells via Nrf2-mediated EMT and ferroptosis
- in-vitro, HCC, HepG2 - in-vitro, Nor, HL7702
Keap1↑, Notably, Withaferin A elevated Keap1 expression to mitigate Nrf2 signaling activation-mediated epithelial to mesenchymal transition (EMT) and ferroptosis-related protein xCT expression
NRF2↓,
EMT↓, Withaferin A suppresses epithelial-to-mesenchymal transition (EMT) in non-small cell lung cancer
TumCP↓, Withaferin A restrains proliferation, invasion, and VM of hepatoma cells while preserving normal hepatocytes
TumCI↓,
selectivity↑, , treatment with Withaferin A ranging from 1 to 100 μM had little effect on cell viability of human normal liver cells (HL-7702 cells), indicating the little cytotoxicity on normal hepatocytes.
*toxicity↓,
ROS↑, Withaferin A strikingly enhanced ROS () and MDA levels (), but reduced the GSH levels (), indicating the induction of ferroptosis by Withaferin A
MDA↑,
GSH↓,
Ferroptosis↑,

1358- Ash,    Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms
- Review, Var, NA
TumCCA↑,
Apoptosis↑,
TumAuto↑,
Ferroptosis↑,
TumCP↓,
CSCs↓,
TumMeta↓,
EMT↓,
angioG↓,
Vim↓,
HSP90↓,
annexin II↓, annexin II proteins directly bind to WA
m-FAM72A↓,
BCR-ABL↓,
Mortalin↓,
NRF2↓,
cMYB↓,
ROS↑, WA inhibits proliferation through ROS-mediated intrinsic apoptosis
ChemoSen↑, WA and cisplatin, WA produced ROS, while cisplatin caused DNA damage, suggesting that lower doses of cisplatin combined with suboptimal doses of WA could achieve the same effect
eff↑, sulforaphane and WA showed synergistic effects on epigenetic modifiers and cell proliferation in breast cancer cells
ChemoSen↑, WA and sorafenib caused G2/M arrest in anaplastic and papillary thyroid cancer cells
ChemoSen↑, combination of WA and 5-FU executed PERK axis-mediated endoplasmic reticulum (ER) stress-induced autophagy and apoptosis
eff↑, WA and carnosol also exhibit a synergistic effect on pancreatic cancer
*BioAv↓, Saurabh by Saurabh et al and Tianming et al reported oral bioavailability values 1.8% and 32.4 ± 4.8%, respectively, in male rats.
ROCK1↓, In another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angi
TumCI↓,
Sp1/3/4↓, Furthermore, WA exerts potent anti-angiogenic activity in vivo.174 In the Ehrlich ascites tumor model, WA exerts its anti-angiogenic activity by reducing the binding of the transcription factor specificity protein 1 (Sp1) to VEGF
VEGF↓, n another study, WA reduces macrophage infiltration and inhibits the expression of protein tyrosine kinase-2 (Pyk2), rho-associated kinase 1 (ROCK1), and VEGF in a hepatocellular carcinoma xenograft model, thereby suppressing tumor invasion and angio
Hif1a↓, Furthermore, WA suppresses the AK4-HIF-1α signaling axis and acts as a potent antimetastatic agent in lung cancer.Citation79
EGFR↓, WA synergistically inhibited wild-type epidermal growth factor receptor (EGFR) lung cancer cell viability

4678- Ash,    Identification of Withaferin A as a Potential Candidate for Anti-Cancer Therapy in Non-Small Cell Lung Cancer
- vitro+vivo, NSCLC, H1975
ROS↑, WA concurrently induced autophagy and apoptosis and the activation of reactive oxygen species (ROS), which plays an upstream role in mediating WA-elicited effects.
AntiTum↑, In vivo research also demonstrated the anti-tumor effect of WA treatment
CSCs↓, We subsequently demonstrated that WA could inhibit the growth of lung CSCs, decrease side population cells, and inhibit lung cancer spheroid-forming capacity
mTOR↓, at least through downregulation of mTOR/STAT3 signaling
STAT3↓,
ChemoSen↑, combination of WA and chemotherapeutic drugs, including cisplatin and pemetrexed, exerted synergistic effects on the inhibition of epidermal growth factor receptor (EGFR) wild-type lung cancer cell viability.
Keap1↑, Interestingly, we found WA treatment gradually increased KEAP1, while it decreased NRF2 in H1975 cells
NRF2↓,

2627- Ba,  Cisplatin,    Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways
RenoP↑, Pretreatment with baicalein ameliorated the cisplatin-induced renal oxidative stress, apoptosis and inflammation and improved kidney injury and function
*iNOS↑, Baicalein inhibited the cisplatin-induced expression of iNOS, TNF-α, IL-6 and mononuclear cell infiltration and concealed redox-sensitive transcription factor NF-κB activation via reduced DNA-binding activity, IκBα phosphorylation and p65 nuclear tra
*TNF-α↓,
*IL6↓,
*NF-kB↓,
*MAPK↓, baicalein markedly attenuated cisplatin-induced p38 MAPK, ERK1/2 and JNK phosphorylation in kidneys
*ERK↓,
*JNK↓,
*antiOx↑, Baicalein also restored the renal antioxidants and increased the amount of total and nuclear accumulation of Nrf2 and downstream target protein, HO-1 in kidneys.
*NRF2↓,
*HO-1↑,
*Cyt‑c∅, inhibited cisplatin-induced apoptosis by suppressing p53 expression, Bax/Bcl-2 imbalance, cytochrome c release and activation of caspase-9, caspase-3 and PARP
*Casp3∅,
*Casp9∅,
*PARP∅,

2617- Ba,    Potential of baicalein in the prevention and treatment of cancer: A scientometric analyses based review
- Review, Var, NA
Ca+2↑, MDA-MB-231 ↑Ca2+
MMP2↓, MDA-MB-231 ↓MMP-2/9
MMP9↓,
Vim↓, ↓Vimentin, ↓SNAIL, ↑E-cadherin, ↓Wnt1, ↓β-catenin
Snail↓,
E-cadherin↑,
Wnt↓,
β-catenin/ZEB1↓,
p‑Akt↓, MCF-7 ↓p-Akt, ↓p-mTOR, ↓NF-κB
p‑mTOR↓,
NF-kB↓,
i-ROS↑, MCF-7 ↑Intracellular ROS, ↓Bcl-2, ↑Bax, ↑cytochrome c, ↑caspase-3/9
Bcl-2↓,
BAX↑,
Cyt‑c↑,
Casp3↑,
Casp9↑,
STAT3↓, 4T1, MDA-MB-231 ↓STAT3, ↓ IL-6
IL6↓,
MMP2↓, HeLa ↓MMP-2, ↓MMP-9
MMP9↓,
NOTCH↓, ↓Notch 1
PPARγ↓, ↓PPARγ
p‑NRF2↓, HCT-116 ↓p-Nrf2
HK2↓, ↓HK2, ↓LDH-A, ↓PDK1, ↓glycolysis, PTEN/Akt/HIF-1α regulation
LDHA↓,
PDK1↓,
Glycolysis↓,
PTEN↑, Furthermore, baicalein inhibited hypoxia-induced Akt phosphorylation by promoting PTEN accumulation, thereby attenuating hypoxia-inducible factor-alpha ( HIF-1a) expression in AGS cells.
Akt↓,
Hif1a↓,
MMP↓, SGC-7901 ↓ΔΨm
VEGF↓, ↓VEGF, ↓VEGFR2
VEGFR2↓,
TOP2↓, ↓Topoisomerase II
uPA↓, ↓u-PA, ↓TIMP1, ↓TIMP2
TIMP1↓,
TIMP2↓,
cMyc↓, ↓β-catenin, ↓c-Myc, ↓cyclin D1, ↓Axin-2
TrxR↓, EL4 ↓Thioredoxin reductase, ↑ASK1,
ASK1↑,
Vim↓, ↓vimentin
ZO-1↑, ↑ZO-1
E-cadherin↑, ↑E-cadherin
SOX2↓, PANC-1, BxPC-3, SW1990 ↓Sox-2, ↓Oct-4, ↓SHH, ↓SMO, ↓Gli-2
OCT4↓,
Shh↓,
Smo↓,
Gli1↓,
N-cadherin↓, ↓N-cadherin
XIAP↓, ↓XIAP

2296- Ba,    The most recent progress of baicalein in its anti-neoplastic effects and mechanisms
- Review, Var, NA
CDK1↓, graphical abstract
Cyc↓,
p27↑,
P21↑,
P53↑,
TumCCA↑, Cell cycle arrest
TumCI↓, Inhibit invastion
MMP2↓,
MMP9↓,
E-cadherin↑,
N-cadherin↓,
Vim↓,
LC3A↑,
p62↓,
p‑mTOR↓,
PD-L1↓,
CAFs/TAFs↓,
VEGF↓,
ROCK1↓,
Bcl-2↓,
Bcl-xL↓,
BAX↑,
ROS↑,
cl‑PARP↑,
Casp3↑,
Casp9↑,
PTEN↑, A549, H460
MMP↓, ↓mitochondrial transmembrane potential, redistribution of cytochrome c,
Cyt‑c↑,
Ca+2↑, ↑Ca2+
PERK↑, ↑PERK, ↑IRE1α, ↑CHOP,
IRE1↑,
CHOP↑,
Copper↑, ↑Cu+2
Snail↓, ↓Snail, ↓vimentin, ↓Twist1,
Vim↓,
Twist↓,
GSH↓, ↑ROS, ↓GSH, ↑MDA, ↓MMP, ↓NRF2, ↓HO-1, ↓GPX4, ↓FTH1, ↑TFR1, ↓p-JAK2, ↓p-STAT3
NRF2↓,
HO-1↓,
GPx4↓,
XIAP↓, ↓Bcl-2, ↓Bcl-xL, ↓XIAP, ↓surviving
survivin↓,
DR5↑, ↑ROS, ↑DR5

5536- BBM,    Regulation of Cell-Signaling Pathways by Berbamine in Different Cancers
- Review, Var, NA
JAK↝, In this review, we comprehensively analyze how berbamine modulates deregulated pathways (JAK/STAT, CAMKII/c-Myc) in various cancers.
STAT3↓, Berbamine physically interacted with STAT3 and inhibited its activation [8].
p‑CaMKII ↓, An orally administered, bioactive small molecule analog of berbamine, tosyl chloride-berbamine (TCB), considerably reduced phosphorylated levels of CaMKIIγ
TGF-β↑, berbamine induces activation of the TGF/SMAD pathway for the effective inhibition of cancer progression.
Smad1↑,
ChemoSen↑, Berbamine enhanced the chemosensitivity of gefitinib against PANC-1 and MIA PaCa-2 cancer cells [8].
RadioS↑, Moreover, berbamine and radiation effectively induced a regression of the tumors in mice subcutaneously injected with FaDu cells [10].
TumCI↓, berbamine-GMO-TPGS nanoparticles showed superior cellular toxicity, as well as an inhibition of migration and invasion in metastatic breast cancer MDA-MB-231,
TumCMig↓,
ROS↑, Berbamine increased the intracellular ROS levels via the downregulation of antioxidative genes such as NRF2, SOD2, GPX-1 and HO-1.
NRF2↓,
SOD2↓,
GPx1↓,
HO-1↓,

5551- BBM,    Berbamine Suppresses the Progression of Bladder Cancer by Modulating the ROS/NF-κB Axis
- vitro+vivo, Bladder, NA
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

2021- BBR,    Berberine: An Important Emphasis on Its Anticancer Effects through Modulation of Various Cell Signaling Pathways
- Review, NA, NA
*antiOx?, Berberine has been noted as a potential therapeutic candidate for liver fibrosis due to its antioxidant and anti-inflammatory activities
*Inflam↓,
Apoptosis↑, Apoptosis induced by berberine in liver cancer cells caused cell cycle arrest at the M/G1 phase and increased the Bax expression
TumCCA↑,
BAX↑,
eff↑, mixture of curcumin and berberine effectively decreases growth in breast cancer cell lines
VEGF↓, berberine also prevented the expression of VEGF
PI3K↓, berberine plays an important role in cancer management through inhibition of the PI3K/AKT/mTOR pathway
Akt↓,
mTOR↓,
Telomerase↓, Berberine decreased the telomerase activity and level of the colorectal cancer cell line,
β-catenin/ZEB1↓, berberine and its derivatives have the ability to inhibit β-catenin/Wnt signaling in tumorigenesis
Wnt↓,
EGFR↓, berberine treatment decreased cell proliferation and epidermal growth factor receptor expression levels in the xenograft model.
AP-1↓, Berberine efficiently targets both the host and the viral factors accountable for cervical cancer development via inhibition of activating protein-1
NF-kB↓, berberine inhibited lung cancer cell growth by concurrently targeting NF-κB/COX-2, PI3K/AKT, and cytochrome-c/caspase signaling pathways
COX2↑,
NRF2↓, Berberine suppresses the Nrf2 signaling-related protein expression in HepG2 and Huh7 cells,
RadioS↑, suggesting that berberine supports radiosensitivity through suppressing the Nrf2 signaling pathway in hepatocellular carcinoma cells
STAT3↓, regulating the JAK–STAT3 signaling pathway
ERK↓, berberine prevented the metastatic potential of melanoma cells via a reduction in ERK activity, and the protein levels of cyclooxygenase-2 by a berberine-caused AMPK activation
AR↓, Berberine reduced the androgen receptor transcriptional activity
ROS↑, In a study on renal cancer, berberine raised the levels of autophagy and reactive oxygen species in human renal tubular epithelial cells derived from the normal kidney HK-2 cell line, in addition to human cell lines ACHN and 786-O cell line.
eff↑, berberine showed a greater apoptotic effect than gemcitabine in cancer cells
selectivity↑, After berberine treatment, it was noticed that berberine showed privileged selectivity towards cancer cells as compared to normal ones.
selectivity↑, expression of caspase-1 and its downstream target Interleukin-1β (IL-1β) was higher in osteosarcoma cells as compared to normal cells
BioAv↓, several studies have been undertaken to overcome the difficulties of low absorption and poor bioavailability through nanotechnology-based strategies.
DNMT1↓, In human multiple melanoma cell U266, berberine can inhibit the expression of DNMT1 and DNMT3B, which leads to hypomethylation of TP53 by altering the DNA methylation level and the p53-dependent signal pathway
cMyc↓, Moreover, berberine suppresses SLC1A5, Na+ dependent transporter expression through preventing c-Myc

1392- BBR,    Based on network pharmacology and experimental validation, berberine can inhibit the progression of gastric cancer by modulating oxidative stress
- in-vitro, GC, AGS - in-vitro, GC, MKN45
TumCG↓,
TumCMig↓,
ROS↑, intracellular
MDA↑, intracellular
SOD↓, intracellular
NRF2↓,
HO-1↓,
Hif1a↓,
EMT↓,
Snail↓,
Vim↓,

1389- BBR,  Lap,    Berberine reverses lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS
- in-vitro, BC, BT474 - in-vitro, BC, AU-565
ChemoSen↑, combination therapy of berberine with lapatinib overcame lapatinib resistance.
Apoptosis↑,
ROS↑,
NRF2↓, Berberine reverses lapatinib resistance by inhibiting the Nrf2 signaling pathway

2756- BetA,    Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathway
- in-vitro, HCC, HUH7 - in-vitro, HCC, H1299
TumCP↓, betulinic acid could suppress proliferation and migration of hepatoma cells, raised ROS level and inhibited antioxidation level in cells
ROS↑,
antiOx↓,
TumCG↓, These findings indicate that betulinic acid has the capacity to significantly impede hepatoma cells growth and migration
TumCMig↓,
NRF2↓, The expression of antioxidant proteins Nrf2, GPX4 and HO-1 was also considerably lower in the BETM and BETH groups than in the Control group
GPx4↓,
HO-1↓,
NCOA4↑, suggesting that betulinic acid activates ferritinophagy by boosting NCOA4 expression and FTH1 degradation.
FTH1↓, betulinic acid groups (10 mg/kg, 20 mg/kg, and 40 mg/kg) greatly boosted LC3II and NCOA4 expressions and suppressed FTH1
Ferritin↑, In summation, betulinic acid decreases antioxidation in tumour tissues from nude mice, inhibits ferritin expression, enhances the expression of ferritinophagy-associated protein, activates ferritinophagy, and initiates ferroptosis in tumour cells.
Ferroptosis↑,
GSH↓, In comparison to the Control group, the betulinic acid groups (10 mg/kg, 20 mg/kg and 40 mg/kg) reduced dramatically GSH and hydroxyl radical inhibition capacity in serum, considerably increased serum Fe2+), and decreased dramatically serum MDA
MDA↓,

5686- BJ,  BRU,    A review of Brucea javanica: metabolites, pharmacology and clinical application
- Review, Var, NA
AntiTum↑, Notably, multiple metabolites in BJ demonstrate anti-tumor effects through various signaling pathways
other↝, well-known metabolites such as Brusatol and Bruceine D.
ChemoSen↑, Multiple clinical studies have demonstrated that the co-administration of BJ with other pharmacological agents in individuals with cancer can enhance therapeutic efficacy, improve patients’ quality of life, and mitigate adverse reactions
QoL↑,
chemoP↑,
*Inflam↓, Brusatol (Zhou et al., 2018) has been shown to reduce inflammation in RAW264.7 cells
NF-kB↓, nhibition of NF-ΚB and ras homolog gene families, member A/rho-associated kinase (RhoA/ROCK) signaling pathways.
TumCP↓, Brusatol has exhibited notable effects in inhibiting proliferation, invasion, and metastasis in a murine model of liver transplantation tumor in humans.
TumCI↓,
TumMeta↓,
Hif1a↓, In colorectal cancer, Brusatol functions by facilitating the degradation process of hypoxia-inducible factor-1 (HIF-1α) (Oh et al., 2017), mediated by prolyl hydroxylase (PHD), while concurrently suppressing NRF2
NRF2↓,
STAT3↓, impede the proliferation and migration of osteosarcoma cells through the inhibition of the STAT3 signaling pathway.
COX2↓, BJO (Lou et al., 2010) induced apoptosis of T24 bladder cancer cells, possibly by upregulating caspase-3 and caspase-9 expression by activating the caspase pathway and inhibiting the NF-ΚB and Cyclooxygenase-2 (COX-2).
Casp3↑,
Casp9↑,
ROS↑, Figure 10
EGFR↓,
NRF2↑, brusatol and dehydrobruceine B (DHB) effectively increased the concentration of reactive oxygen species (ROS) by activating the NRF2 pathway

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

738- Bor,    Borax induces ferroptosis of glioblastoma by targeting HSPA5/NRF2/GPx4/GSH pathways
- in-vitro, GBM, U251 - in-vitro, GBM, A172 - in-vitro, Nor, SVGp12
TumCP↓,
GPx4↓, borax treatment decreased GPx4, GSH, HSPA5 and NRF2 levels in U251 and A172 cells while increasing MDA levels and caspase‐3/7 activity.
GSH↓,
HSP70/HSPA5↓,
NRF2↓,
MDA↑,
Casp3↑,
Casp7↑,
Ferroptosis↑, Consequently, borax may induce ferroptosis in GBM cells
selectivity↑, Treating SVG cells with borax concentrations ranging from 0 to 800 μM for 24 h did not result in a significant reduction in viability compared to the control group

5695- BRU,    Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism
- in-vitro, Lung, A549
NRF2↓, Here, we report the identification of brusatol as a unique inhibitor of the Nrf2 pathway that sensitizes a broad spectrum of cancer cells and A549 xenografts to cisplatin and other chemotherapeutic drugs.
ChemoSen↑,
Apoptosis↑, induced apoptosis, reduced cell proliferation, and inhibited tumor growth more substantially when compared with cisplatin treatment alone.
TumCP↓,
TumCG↓,
MRP1↓, the protein level of Nrf2-target genes, including γGCS, MRP1, and MRP2, was also reduced in a dose-dependent manner, whereas only a slight reduction in NQO1 was observed
GSH↓, Brusatol Treatment Decreased Glutathione Levels and Increased the Intracellular Concentration of Cisplatin.
cMyc↓, inhibition of both Nrf2 and c-Myc by brusatol

5691- BRU,    Brusatol Inhibits Proliferation, Migration, and Invasion of Nonsmall Cell Lung Cancer PC-9 Cells
- in-vitro, Lung, PC9 - in-vitro, Lung, H1975
TumCP↓, brusatol suppressed PC-9 cell proliferation, migration, and invasion, as well as induced apoptosis,
TumCMig↓,
TumCI↓,
Apoptosis↑,
EGFR↓, downregulation of epidermal growth factor receptor (EGFR), β-catenin, Akt, and STAT3
β-catenin/ZEB1↓,
Akt↓,
STAT3↓,
TumMeta↓, inhibiting the proliferative capacity and metastatic potential of PC-9 cells.
ChemoSen↑, Ren et al. found that brusatol enhanced patient sensitivity to chemotherapeutics by inhibiting the cellular defense mechanism mediated by nuclear factor (erythroid-derived 2)-like 2 protein (Nrf2), which promoted the degradation of Nrf2
NRF2↓,
Akt↓, Brusatol also induced cancer cell apoptosis by inhibiting the Akt/mTOR pathway.[5]
mTOR↓,

5693- BRU,    Brusatol provokes a rapid and transient inhibition of Nrf2 signaling and sensitizes mammalian cells to chemical toxicity-implications for therapeutic targeting of Nrf2
- in-vivo, HCC, NA
NRF2↓, we show that brusatol provokes a rapid and transient depletion of Nrf2 protein
eff↑, brusatol is capable of sensitizing mammalian cells to chemical stress.
p‑MAPK↑, brusatol provoked a rapid increase in the phosphorylation of p38 MAPK, AKT, ERK1/2, and JNK1/2 in parallel with depletion of Nrf2
p‑Akt↑,
p‑ERK↑,
p‑JNK↑,

5694- BRU,    Brusatol overcomes chemoresistance through inhibition of protein translation
- in-vitro, Lung, A549
NRF2↓, brusatols mode of action is not through direct inhibition of the NRF2 pathway, but through the inhibition of both cap-dependent and cap-independent protein translation, which has an impact on many short-lived proteins, including NRF2.
P53↓, After a 4 h treatment, both brusatol and bruceantin reduced the protein levels of NRF2, p53, and p21 in a dose-dependent manner
P21↓,

5696- BRU,    The Nrf2 inhibitor brusatol is a potent antitumour agent in an orthotopic mouse model of colorectal cancer
- in-vitro, CRC, HCT116
NRF2↓, brusatol, which is known to inhibit Nrf2, decreased viability and sensitised cells to irinotecan toxicity.
tumCV↓,
ChemoSen↑, Brusatol has been shown to inhibit Nrf2 and enhance chemosensitivity in a number of cancer cell lines

5697- BRU,    Brusatol, a Nrf2 Inhibitor Targets STAT3 Signaling Cascade in Head and Neck Squamous Cell Carcinoma
- in-vitro, HNSCC, NA
NRF2↓, Brusatol, a Nrf2 Inhibitor
STAT3↓, we identified brusatol (BT) as a potential blocker of STAT3 signaling pathway in diverse HNSCC cells.
proCasp3↑, promoted procaspase-3 and PARP cleavage, and downregulated the mRNA and protein expression of diverse proteins (Bcl-2, Bcl-xl, survivin) in HNSCC cells.
cl‑PARP↑,
Bcl-2↓,
Bcl-xL↓,
survivin↓,
Hif1a↓, BT also induced the degradation of HIF-1α
cMyc↓, BT suppressed c-Myc expression
JNK↑, BT was found to activate JNK and p38 MAPK pathways with concurrent inhibition of proinflammatory signaling pathways such as NF-κB and STAT3
MAPK↑,
tumCV↓, BT Reduced the Cell Viability of HNSCC Cells
ROS∅, BT treatment did not significantly alter the level of ROS

5698- BRU,    Brusatol suppresses STAT3-driven metastasis by downregulating epithelial-mesenchymal transition in hepatocellular carcinoma
- in-vitro, HCC, NA
TumCMig↓, Brusatol affects migration and invasion ability of HCC cells.
EMT↓, Brusatol affects EMT process through modulation of STAT3 activation pathway.
STAT3↓, BT concentration-dependently inhibited constitutive STAT3 activation
E-cadherin↑, BT treatment restored the expression of Occludin, E-cadherin (epithelial markers) while suppressing the levels of different mesenchymal markers in HCC cells and tumor tissues.
NRF2↓, Brusatol (BT) is a natural quassinoid that has been demonstrated as an inhibitor of nuclear factor erythroid 2-related factor-2 (Nrf-2) by several research groups
ChemoSen↑, BT can interfere with Nrf-2 signaling in cancer cells to enhance the chemotherapeutic potential of paclitaxel, cisplatin, 5-fluorouracil, gemcitabine, carboplatin, and etoposide
RadioS↑, and also increase the radiosensitivity of lung cancer cells
DNAdam↑, BT disrupted Nrf-2 dependent transcriptional activity and induced oxidative DNA damage [33].
TumCMig↓, BT suppresses migration as well as invasion in HCC cells
TumCI↓,
toxicity↓, BT treatment did not impart notable toxicity in tested mice

5699- BRU,  BJ,    Identification of the Brucea javanica Constituent Brusatol as a EGFR-Tyrosine Kinase Inhibitor in a Cell-Free Assay
- in-vitro, Lung, A549
EGFR↓, brusatol inhibits EGFR-TK
ChemoSen↑, is administered to cancer patients in combination with chemotherapy in the form of two patented galenic preparations, i.e., BJO emulsion injection and BJO soft capsule.5
NRF2↓, brusatol, with the inhibition of Nrf2 as the most evident
STAT3↓, inhibition of STAT3,16,29,37 PI3K/Akt/mTOR,18,22,38,39 RhoA/ROCK,20 HIF1α,27,40 and Skp1
PI3K↓,
Akt↓,
mTOR↓,
ROCK1↓,
Hif1a↓,

5700- BRU,    Brusatol modulates the Nrf2/GCLC pathway to enhance ferroptosis in the treatment of oral squamous cell carcinoma
- in-vitro, Oral, CAL27
TumCG↓, we found that brusatol (BRT) can effectively inhibit the growth rate of the nude mouse heterotopic transplantation tumor model constructed with Cal-27 cells.
Ferroptosis↑, Secondly, it was proved that brusatol (BRT) can promote the ferroptosis of Cal-27 cells, reduce their survival rate, and inhibit their growth and migration capabilities.
TumCMig↓,
NRF2↓, Nrf2, as a key factor in facilitating ferroptosis by brusatol (BRT),
i-GSH↓, leading to depletion of intracellular GSH, accumulation of Fe2+ and ROS, and the occurrence of ferroptosis in Cal-27 cells.
Iron↑,
ROS↑,

5703- BRU,    Brusatol Enhances the Radiosensitivity of A549 Cells by Promoting ROS Production and Enhancing DNA Damage
- in-vitro, Lung, H1299 - in-vitro, Lung, A549 - in-vitro, Lung, H460
NRF2↓, We found that the Nrf2 inhibitor, brusatol, could prevent the increase and accumulation of Nrf2 after exposure to irradiation.
RadioS↑,
DNAdam↑, A549 cells became sensitive to irradiation, suffering severe DNA damage.
ROS↑, Combination treatment with brusatol and ionizing radiation (IR) can distinctly increase the level of reactive oxygen species in A549 cells

5701- BRU,    Brusatol induced ferroptosis in osteosarcoma cells by modulating the Keap1/Nrf2/SLC7A11 signaling pathway
- in-vitro, OS, NA
TumMeta↓, Brucea javanica and Brucea sumatrana, has been shown to possess the potential to inhibit tumor metastasis and proliferation
TumCP↓,
ROS↑, Bru induced mitochondrial dysfunction and a marked increase in reactive oxygen species in OS cells.
Ferroptosis↑, Bru exerts its anti-OS effects by inducing ferroptosis through the regulation of the Keap1/Nrf2/SLC7A11 signaling pathway.
NRF2↓,
ChemoSen↑, we found that the combination of Bru and the chemotherapeutic agent doxorubicin (DOX) significantly enhanced DOX's anti-OS efficacy by activating apoptotic pathways.

2590- CHr,    Chrysin suppresses proliferation, migration, and invasion in glioblastoma cell lines via mediating the ERK/Nrf2 signaling pathway
- in-vitro, GBM, T98G - in-vitro, GBM, U251 - in-vitro, GBM, U87MG
TumCP↓, Chrysin inhibited the proliferation, migration, and invasion capacity of glioblastoma cells in dose- and time-dependent manners.
TumCMig↓,
TumCI↓,
NRF2↓, chrysin deactivated the Nrf2 signaling pathway by decreasing the translocation of Nrf2 into the nucleus
HO-1↓, suppressing the expression of hemeoxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1
NADPH↓,
ERK↓, Chrysin treatment downregulates the Nrf2 pathway via inhibition of ERK signaling

2591- CHr,  doxoR,    Chrysin enhances sensitivity of BEL-7402/ADM cells to doxorubicin by suppressing PI3K/Akt/Nrf2 and ERK/Nrf2 pathway
- in-vitro, HCC, Bel-7402
NRF2↓, chrysin is a potent Nrf2 inhibitor which sensitizes BEL-7402/ADM cells to ADM
ChemoSen↑, chrysin may be an effective adjuvant sensitizer to reduce anticancer drug resistance by down-regulating Nrf2 signaling pathway.
HO-1↓, Consequently, expression of Nrf2-downstream genes HO-1, AKR1B10, and MRP5 were reduced

2781- CHr,  PBG,    Chrysin a promising anticancer agent: recent perspectives
- Review, Var, NA
PI3K↓, It can block Phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling in different animals against various cancers
Akt↓,
mTOR↓,
MMP9↑, Chrysin strongly suppresses Matrix metalloproteinase-9 (MMP-9), Urokinase plasminogen activator (uPA) and Vascular endothelial growth factor (VEGF), i.e. factors that can cause cancer
uPA↓,
VEGF↓,
AR↓, Chrysin has the ability to suppress the androgen receptor (AR), a protein necessary for prostate cancer development and metastasis
Casp↑, starts the caspase cascade and blocks protein synthesis to kill lung cancer cells
TumMeta↓, Chrysin significantly decreased lung cancer metastasis i
TumCCA↑, Chrysin induces apoptosis and stops colon cancer cells in the G2/M cell cycle phase
angioG↓, Chrysin prevents tumor growth and cancer spread by blocking blood vessel expansion
BioAv↓, Chrysin’s solubility, accessibility and bioavailability may limit its medical use.
*hepatoP↑, As chrysin reduced oxidative stress and lipid peroxidation in rat liver cells exposed to a toxic chemical agent.
*neuroP↑, Protecting the brain against oxidative stress (GPx) may be aided by increasing levels of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GPx).
*SOD↑,
*GPx↑,
*ROS↓, A decrease in oxidative stress and an increase in antioxidant capacity may result from chrysin’s anti-inflammatory properties
*Inflam↓,
*Catalase↑, Supplementation with chrysin increased the activity of antioxidant enzymes like SOD and catalase and reduced the levels of oxidative stress markers like malondialdehyde (MDA) in the colon tissue of the rats.
*MDA↓, Antioxidant enzyme activity (SOD, CAT) and oxidative stress marker (MDA) levels were both enhanced by chrysin supplementation in mouse liver tissue
ROS↓, reduction of reactive oxygen species (ROS) and oxidative stress markers in the cancer cells further indicated the antioxidant activity of chrysin
BBB↑, After crossing the blood-brain barrier, it has been shown to accumulate there
Half-Life↓, The half-life of chrysin in rats is predicted to be close to 2 hours.
BioAv↑, Taking chrysin with food may increase the effectiveness of the supplement: increased by a factor of 1.8 when taken with a high-fat meal
ROS↑, In contrast to 5-FU/oxaliplatin, chrysin increases the production of reactive oxygen species (ROS), which in turn causes autophagy by stopping Akt and mTOR from doing their jobs
eff↑, mixture of chrysin and cisplatin caused the SCC-25 and CAL-27 cell lines to make more oxygen free radicals. After treatment with chrysin, cisplatin, or both, the amount of reactive oxygen species (ROS) was found to have gone up.
ROS↑, When reactive oxygen species (ROS) and calcium levels in the cytoplasm rise because of chrysin, OC cells die.
ROS↑, chrysin is the cause of death in both types of prostate cancer cells. It does this by depolarizing mitochondrial membrane potential (MMP), making reactive oxygen species (ROS), and starting lipid peroxidation.
lipid-P↑,
ER Stress↑, when chrysin is present in DU145 and PC-3 cells, the expression of a group of proteins that control ER stress goes up
NOTCH1↑, Chrysin increased the production of Notch 1 and hairy/enhancer of split 1 at the protein and mRNA levels, which stopped cells from dividing
NRF2↓, Not only did chrysin stop Nrf2 and the genes it controls from working, but it also caused MCF-7 breast cancer cells to die via apoptosis.
p‑FAK↓, After 48 hours of treatment with chrysin at amounts between 5 and 15 millimoles, p-FAK and RhoA were greatly lowered
Rho↓,
PCNA↓, Lung histology and immunoblotting studies of PCNA, COX-2, and NF-B showed that adding chrysin stopped the production of these proteins and maintained the balance of cells
COX2↓,
NF-kB↓,
PDK1↓, After the chrysin was injected, the genes PDK1, PDK3, and GLUT1 that are involved in glycolysis had less expression
PDK3↑,
GLUT1↓,
Glycolysis↓, chrysin stops glycolysis
mt-ATP↓, chrysin inhibits complex II and ATPases in the mitochondria of cancer cells
Ki-67↓, the amounts of Ki-67, which is a sign of growth, and c-Myc in the tumor tissues went down
cMyc↓,
ROCK1↓, (ROCK1), transgelin 2 (TAGLN2), and FCH and Mu domain containing endocytic adaptor 2 (FCHO2) were much lower.
TOP1↓, DNA topoisomerases and histone deacetylase were inhibited, along with the synthesis of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and (IL-1 beta), while the activity of protective signaling pathways was increased
TNF-α↓,
IL1β↓,
CycB/CCNB1↓, Chrysin suppressed cyclin B1 and CDK2 production in order to stop cancerous growth.
CDK2↓,
EMT↓, chrysin treatment can also stop EMT
STAT3↓, chrysin block the STAT3 and NF-B pathways, but it also greatly reduced PD-L1 production both in vivo and in vitro.
PD-L1↓,
IL2↑, chrysin increases both the rate of T cell growth and the amount of IL-2

2782- CHr,    Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives
- Review, Var, NA - Review, Stroke, NA - Review, Park, NA
*antiOx↑, antioxidant, anti-inflammatory, hepatoprotective, neuroprotective
*Inflam↓, inhibitory effect of chrysin on inflammation and oxidative stress is also important in Parkinson’s disease
*hepatoP↑,
*neuroP↑,
*BioAv↓, Accumulating data demonstrates that poor absorption, rapid metabolism, and systemic elimination are responsible for poor bioavailability of chrysin in humans that, subsequently, restrict its therapeutic effects
*cardioP↑, cardioprotective [69], lipid-lowering effect [70]
*lipidLev↓,
*RenoP↑, Renoprotective
*TNF-α↓, chrysin reduces levels of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2).
*IL2↓,
*PI3K↓, induction of the PI3K/Akt signaling pathway by chrysin contributes to a reduction in oxidative stress and inflammation during cerebral I/R injury
*Akt↓,
*ROS↓,
*cognitive↑, Chrysin (25, 50, and 100 mg/kg) improves cognitive capacity, inflammation, and apoptosis to ameliorate traumatic brain injury
eff↑, chrysin and silibinin is beneficial in suppressing breast cancer malignancy via decreasing cancer proliferation
cycD1/CCND1↓, chrysin and silibinin induced cell cycle arrest via down-regulation of cyclin D1 and hTERT
hTERT/TERT↓,
VEGF↓, Administration of chrysin is associated with the disruption of hypoxia-induced VEGF gene expression
p‑STAT3↓, chrysin is capable of reducing STAT3 phosphorylation in hypoxic conditions without affecting the HIF-1α protein level.
TumMeta↓, chrysin is a potent agent in suppressing metastasis and proliferation of breast cancer cells during hypoxic conditions
TumCP↓,
eff↑, combination therapy of breast cancer cells using chrysin and metformin exerts a synergistic effect and is more efficient compared to chrysin alone
eff↑, combination of quercetin and chrysin reduced levels of pro-inflammatory factors, such as IL-1β, Il-6, TNF-α, and IL-10, via NF-κB down-regulation.
IL1β↓,
IL6↓,
NF-kB↓,
ROS↑, after chrysin administration, an increase occurs in levels of ROS that, subsequently, impairs the integrity of the mitochondrial membrane, leading to cytochrome C release and apoptosis induction
MMP↓,
Cyt‑c↑,
Apoptosis↑,
ER Stress↑, in addition to mitochondria, ER can also participate in apoptosis
Ca+2↑, Upon chrysin administration, an increase occurs in levels of ROS and cytoplasmic Ca2+ that mediate apoptosis induction in OC cells
TET1↑, In MKN45 cells, chrysin promotes the expression of TET1
Let-7↑, Chrysin is capable of promoting the expression of miR-9 and Let-7a as onco-suppressor factors in cancer to inhibit the proliferation of GC cells
Twist↓, Down-regulation of NF-κB, and subsequent decrease in Twist/EMT are mediated by chrysin administration, negatively affecting cervical cancer metastasis
EMT↓,
TumCCA↑, nduction of cell cycle arrest and apoptosis via up-regulation of caspase-3, caspase-9, and Bax are mediated by chrysin
Casp3↑,
Casp9↑,
BAX↑,
HK2↓, Chrysin administration (15, 30, and 60 mM) reduces the expression of HK-2 in hepatocellular carcinoma (HCC) cells to impair glucose uptake and lactate production.
GlucoseCon↓,
lactateProd↓,
Glycolysis↓, In addition to glycolysis metabolism impairment, the inhibitory effect of chrysin on HK-2 leads to apoptosis
SHP1↑, upstream modulator of STAT3 known as SHP-1 is up-regulated by chrysin
N-cadherin↓, Furthermore, N-cadherin and E-cadherin are respectively down-regulated and up-regulated upon chrysin administration in inhibiting melanoma invasion
E-cadherin↑,
UPR↑, chrysin substantially diminishes survival by ER stress induction via stimulating UPR, PERK, ATF4, and elF2α
PERK↑,
ATF4↑,
eIF2α↑,
RadioS↑, Irradiation combined with chrysin exerts a synergistic effect
NOTCH1↑, Irradiation combined with chrysin exerts a synergistic effect
NRF2↓, in reducing Nrf2 expression, chrysin down-regulates the expression of ERK and PI3K/Akt pathways—leading to an increase in the efficiency of doxorubicin in chemotherapy
BioAv↑, chrysin at the tumor site by polymeric nanoparticles leads to enhanced anti-tumor activity, due to enhanced cellular uptake
eff↑, Chrysin- and curcumin-loaded nanoparticles significantly promote the expression of TIMP-1 and TIMP-2 to exert a reduction in melanoma invasion

2785- CHr,    Emerging cellular and molecular mechanisms underlying anticancer indications of chrysin
- Review, Var, NA
*NF-kB↓, suppressed pro-inflammatory cytokine expression and histamine release, downregulated nuclear factor kappa B (NF-kB), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS)
*COX2↓,
*iNOS↓,
angioG↓, upregulated apoptotic pathways [28], inhibited angiogenesis [29] and metastasis formation
TOP1↓, suppressed DNA topoisomerases [31] and histone deacetylase [32], downregulated tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β)
HDAC↓,
TNF-α↓,
IL1β↓,
cardioP↑, promoted protective signaling pathways in the heart [34], kidney [35] and brain [8], decreased cholesterol level
RenoP↑,
neuroP↑,
LDL↓,
BioAv↑, bioavailability of chrysin in the oral route of administration was appraised to be 0.003–0.02% [55], the maximum plasma concentration—12–64 nM
eff↑, Chrysin alone and potentially in combination with metformin decreased cyclin D1 and hTERT gene expression in the T47D breast cancer cell line
cycD1/CCND1↓,
hTERT/TERT↓,
MMP-10↓, Chrysin pretreatment inhibited MMP-10 and Akt signaling pathways
Akt↓,
STAT3↓, Chrysin declined hypoxic survival, inhibited activation of STAT3, and reduced VEGF expression in hypoxic cancer cells
VEGF↓,
EGFR↓, chrysin to inhibit EGFR was reported in a breast cancer stem cell model [
Snail↓, chrysin downregulated MMP-10, reduced snail, slug, and vimentin expressions increased E-cadherin expression, and inhibited Akt signaling pathway in TNBC cells, proposing that chrysin possessed a reversal activity on EMT
Slug↓,
Vim↓,
E-cadherin↑,
eff↑, Fabrication of chrysin-attached to silver and gold nanoparticles crossbred reduced graphene oxide nanocomposites led to augmentation of the generation of ROS-induced apoptosis in breast cancer
TET1↑, Chrysin induced augmentation in TET1
ROS↑, Pretreatment with chrysin induced ROS formation, and consecutively, inhibited Akt phosphorylation and mTOR.
mTOR↓,
PPARα↓, Chrysin inhibited mRNA expression of PPARα
ER Stress↑, ROS production by chrysin was the critical mediator behind induction of ER stress, leading to JNK phosphorylation, intracellular Ca2+ release, and activation of the mitochondrial apoptosis pathway
Ca+2↑,
ERK↓, reduced protein expression of p-ERK/ERK
MMP↑, Chrysin pretreatment led to an increase in mitochondrial ROS creation, swelling in isolated mitochondria from hepatocytes, collapse in MMP, and release cytochrome c.
Cyt‑c↑,
Casp3↑, Chrysin could elevate caspase-3 activity in the HCC rats group
HK2↓, chrysin declined HK-2 combined with VDAC-1 on mitochondria
NRF2↓, chrysin inhibited the Nrf2 expression and its downstream genes comprising AKR1B10, HO-1, and MRP5 by quenching ERK and PI3K-Akt pathway
HO-1↓,
MMP2↓, Chrysin pretreatment also downregulated MMP2, MMP9, fibronectin, and snail expression
MMP9↓,
Fibronectin↓,
GRP78/BiP↑, chrysin induced GRP78 overexpression, spliced XBP-1, and eIF2-α phosphorylation
XBP-1↓,
p‑eIF2α↑,
*AST↓, Chrysin administration significantly reduced AST, ALT, ALP, LDH and γGT serum activities
ALAT↓,
ALP↓,
LDH↓,
COX2↑, chrysin attenuated COX-2 and NFkB p65 expression, and Bcl-xL and β-arrestin levels
Bcl-xL↓,
IL6↓, Reduction in IL-6 and TNF-α and augmentation in caspases-9 and 3 were observed due to chrysin supplementation.
PGE2↓, Chrysin induced entire suppression NF-kB, COX-2, PG-E2, iNOS as well.
iNOS↓,
DNAdam↑, Chrysin induced apoptosis of cells by causing DNA fragmentation and increasing the proportions of DU145 and PC-3 cells
UPR↑, Also, it induced ER stress via activation of UPR proteins comprising PERK, eIF2α, and GRP78 in DU145 and PC-3 cells.
Hif1a↓, Chrysin increased the ubiquitination and degradation of HIF-1α by increasing its prolyl hydroxylation
EMT↓, chrysin was effective in HeLa cell by inhibiting EMT and CSLC properties, NF-κBp65, and Twist1 expression
Twist↓,
lipid-P↑, Chrysin disrupted intracellular homeostasis by altering MMP, cytosolic Ca (2+) levels, ROS generation, and lipid peroxidation, which plays a role in the death of choriocarcinoma cells.
CLDN1↓, Chrysin decreased CLDN1 and CLDN11 expression in human lung SCC
PDK1↓, Chrysin alleviated p-Akt and inhibited PDK1 and Akt
IL10↓, Chrysin inhibited cytokines release, TNF-α, IL-1β, IL-10, and IL-6 induced by Ni in A549 cells.
TLR4↓, Chrysin suppressed TLR4 and Myd88 mRNA and protein expression.
NOTCH1↑, Chrysin inhibited tumor growth in ATC both in vitro and in vivo through inducing Notch1
PARP↑, Pretreating cells with chrysin increased cleaved PARP, cleaved caspase-3, and declined cyclin D1, Mcl-1, and XIAP.
Mcl-1↓,
XIAP↓,

2786- CHr,    Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives
- Review, Var, NA
Apoptosis↑, chrysin inhibits cancer growth through induction of apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and metastasis without causing any toxicity and undesirable side effects to normal cells
TumCCA↑,
angioG↓,
TumCI↓,
TumMeta↑,
*toxicity↓,
selectivity↑,
chemoPv↑, Induction of phase II detoxification enzymes, such as glutathione S-transferase (GST) or NAD(P)H:quinone oxidoreductase (QR) is one of the major mechanism of protection against initiation of carcinogenesis
*GSTs↑,
*NADPH↑,
*GSH↑, upregulation of antioxidant and carcinogen detoxification enzymes (glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), GST and QR)
HDAC8↓, inhibits of HDAC8 enzymatic activity
Hif1a↓, Prostate DU145: Inhibits HIF-1a expression through Akt signaling and abrogation of VEGF expression
*ROS↓, chrysin (20 and 40 mg/kg) was shown to exhibit chemopreventive activity by ameliorating oxidative stress and inflammation via NF-kB pathway
*NF-kB↓,
SCF↓, Chrysin has also been reported to have the ability to abolish the stem cell factor (SCF)/c-Kit signaling in human myeloid leukemia cells by preventing the PI3 K pathway
cl‑PARP↑, (PARP) and caspase-3 and concurrently decreasing pro-survival proteins survivin and XIAP
survivin↓,
XIAP↓,
Casp3↑, activation of caspase-3 and -9.
Casp9↑,
GSH↓, chrysin sustains a significant depletion of intracellular GSH concentrations in human NSCLC cells
ChemoSen↑, chrysin potentiates cisplatin toxicity, in part, via synergizing pro-oxidant effects of cisplatin by inducing mitochondrial dysfunction, and by depleting cellular GSH, an important antioxidant defense
Fenton↑, ability to participate in a fenton type chemical reaction
P21↑, upregulation of p21 independent of p53 status and decrease in cyclin D1, CDK2 protein levels
P53↑,
cycD1/CCND1↓,
CDK2↓,
STAT3↓, chrysin inhibits angiogenesis through inhibition of STAT3 and VEGF release mediated by hypoxia through Akt signaling pathway
VEGF↓,
Akt↓,
NRF2↓, Chrysin treatment significantly reduced nrf2 expression in cells at both the mRNA and protein levels through down-regulation of PI3K-Akt and ERK pathways.

1410- CUR,    Curcumin induces ferroptosis and apoptosis in osteosarcoma cells by regulating Nrf2/GPX4 signaling pathway
- vitro+vivo, OS, MG63
tumCV↓,
Apoptosis↑,
TumCG↓,
NRF2↓, after treatment with curcumin, Nrf2 and GPX4 levels were significantly decreased
GPx4↓,
HO-1↓,
xCT↓, SLC7A11
ROS↑, our results revealed that after treatment with curcumin, ROS and MDA levels were significantly increased while GSH levels were decreased
MDA↑,
GSH↓,

1844- dietFMD,    Unlocking the Potential: Caloric Restriction, Caloric Restriction Mimetics, and Their Impact on Cancer Prevention and Treatment
- Review, NA, NA
Risk↓, CRMs were well tolerated, and metformin and aspirin showed the most promising effect in reducing cancer risk in a selected group of patients.
AMPK↑, the increased AMP levels activate AMPK
Akt↓, This activation results in the inhibition of AKT and mTOR pathways
mTOR↓,
SIRT1↑, energy deficit also activates the SIRT pathways, which downregulates HIF1α, and the Nrf2 pathway
Hif1a↓,
NRF2↓,
SOD↑, enhances antioxidant defenses (e.g., superoxide dismutase SOD1 and SOD2)
ROS↑, Additionally, in prostate cancer (PC) [55] and triple-negative breast cancer (TNBC) [56] cell lines glucose restriction (GR) has been shown to trigger an increase in ROS, leading to cell death.
IGF-1↓, CR decreases poor prognosis markers such as IGF1, pAKT, and PI3K
p‑Akt↓,
PI3K↑,
GutMicro↑, induces changes in the gut microbiome linked to anti-tumor effects
OS↑, Incorporating a nutraceutical regimen like CR or KD with CT has reduced tumor growth and relapse and improved the survival rate
eff↝, type of dietary intervention, with FMD being the first option, followed by KD and CR last. FMD has been considered the most cost-effective and applicable because it does not completely restrict food intake.
ROS↑, findings consistently indicating that dietary restrictions render highly proliferative tumor cells more susceptible to oxidative damage
TumCCA↑, CR has been reported to induce cell cycle arrest in the G0/G1 phases , enabling cells to undergo DNA repair more efficiently and diminishing DNA damage by CRT
*DNArepair↑,
DNAdam↑, In contrast, tumoral cells, which have an altered cell cycle, are unable to repair DNA, leading to cell death

5007- DSF,  Cu,    Nrf2/HO-1 Alleviates Disulfiram/Copper-Induced Ferroptosis in Oral Squamous Cell Carcinoma
- vitro+vivo, Oral, NA
AntiTum↑, Accumulating evidence indicates that the disulfiram/copper complex (DSF/Cu) has been shown to have potent antitumor activity against various cancers.
TumCP↓, DSF/Cu reduced the proliferation and clonogenicity of OSCC cells.
Ferroptosis↑, DSF/Cu also induced ferroptosis
Iron↑, Importantly, we confirmed that DSF/Cu could increase the free iron pool, enhance lipid peroxidation, and eventually result in ferroptosis cell death.
lipid-P↑,
NRF2↓, DSF/Cu inhibited the xenograft growth of OSCC cells by suppressing the expression of Nrf2/HO-1.
HO-1↓,

5009- DSF,  Cu,    Activation of Oxidative Stress and Down-Regulation of Nuclear Factor Erythroid 2-Related Factor May Be Responsible for Disulfiram/Copper Complex Induced Apoptosis in Lymphoid Malignancy Cell Lines
- vitro+vivo, lymphoma, NA
AntiTum↑, Disulfiram (DS), an antialcoholism drug, demonstrates strong antitumor activity in a copper (Cu)-dependent manner.
ROS↑, DS/Cu induces reactive oxidative stress (ROS) which activates stress related signaling pathway (c-Jun-amino-terminal kinase, JNK).
JNK↑,
NRF2↓, Nrf2 expression was increased when Raji cells were treated for less than 12h and decreased after 18h or 24h treatment
eff↓, N-acetyl-L-cysteine (NAC), an antioxidant, can partially attenuate DS/Cu complex-induced apoptosis
TumCD↑, Therefore the DS/Cu induced ROS may be higher than that antioxidant factors could protect and thus the Nrf2-mediated cellular survival mechanism was disabled through down regulation of Nrf2 to allow initiation of death process.

5006- DSF,  Cu,    Disulfiram targeting lymphoid malignant cell lines via ROS-JNK activation as well as Nrf2 and NF-kB pathway inhibition
- vitro+vivo, lymphoma, NA
TumCD↑, n combination with a low concentration (1 μM) of Cu2+, DS induced cytotoxicity in Raji cells with an IC50 of 0.085 ± 0.015 μM and in Molt4 cells with an IC50 of 0.435 ± 0.109 μM.
TumCP↑, DS/Cu inhibits the proliferation of Raji cells in vivo.
Apoptosis↑, After exposure to DS (3.3 μM)/Cu (1 μM) for 24 hours, apoptosis was detected in 81.03 ± 7.91% of Raji cells
NRF2↓, After 24 h exposure, DS/Cu inhibits Nrf2 expression.
ROS↑, DS/Cu induced ROS generation.
p‑JNK↑, DS/Cu induced phosphorylation of JNK and inhibits p65 expression as well as Nrf2 expression both in vitro and in vivo.
p65↓,
eff↓, N-acetyl-L-cysteine (NAC), an antioxidant, can partially attenuate DS/Cu complex-induced apoptosis and block JNK activation in vitro.
NF-kB↓, Moreover, ROS-related activation of JNK pathway and inhibition of NF-κB and Nrf2 may also contribute to the DS/Cu induced apoptosis.


Showing Research Papers: 1 to 50 of 105
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* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 105

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   Catalase↓, 1,   Copper↑, 1,   Fenton↑, 2,   Ferroptosis↑, 9,   GPx1↓, 2,   GPx4↓, 4,   GSH↓, 8,   i-GSH↓, 1,   GSTP1/GSTπ↓, 1,   HO-1↓, 13,   Iron↑, 2,   i-Iron↓, 1,   Keap1↑, 2,   lipid-P↑, 4,   MDA↓, 1,   MDA↑, 4,   NQO1↓, 1,   NRF2↓, 49,   NRF2↑, 2,   p‑NRF2↓, 1,   ROS↓, 2,   ROS↑, 34,   ROS∅, 1,   i-ROS↑, 1,   SIRT3↓, 1,   SOD↓, 3,   SOD↑, 2,   SOD1↑, 1,   SOD2↓, 2,   TrxR↓, 1,   xCT↓, 1,  

Metal & Cofactor Biology ⓘ

Ferritin↑, 1,   FTH1↓, 1,   NCOA4↑, 1,  

Mitochondria & Bioenergetics ⓘ

mt-ATP↓, 1,   BCR-ABL↓, 1,   MMP↓, 5,   MMP↑, 2,   Mortalin↓, 1,   XIAP↓, 5,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 2,   cMyc↓, 6,   GlucoseCon↓, 2,   Glycolysis↓, 3,   HK2↓, 3,   lactateProd↓, 1,   LDH↓, 1,   LDHA↓, 1,   LDL↓, 1,   NADPH↓, 1,   NADPH↑, 1,   PDK1↓, 5,   PDK3↑, 1,   PPARα↓, 1,   PPARγ↓, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 14,   p‑Akt↓, 3,   p‑Akt↑, 1,   Apoptosis↑, 13,   ASK1↑, 1,   BAX↑, 4,   Bax:Bcl2↑, 3,   Bcl-2↓, 5,   Bcl-xL↓, 3,   Casp↑, 2,   Casp12↑, 1,   Casp3↑, 8,   proCasp3↑, 1,   Casp7↑, 1,   Casp9↑, 7,   CK2↓, 2,   Cyt‑c↑, 6,   DR5↑, 1,   Ferroptosis↑, 9,   hTERT/TERT↓, 2,   iNOS↓, 1,   JNK↑, 2,   p‑JNK↑, 2,   MAPK↑, 1,   p‑MAPK↑, 1,   Mcl-1↓, 1,   p27↑, 4,   p38↑, 2,   survivin↓, 4,   Telomerase↓, 3,   TumCD↑, 3,  

Kinase & Signal Transduction ⓘ

p‑CaMKII ↓, 1,   HER2/EBBR2↓, 1,   Sp1/3/4↓, 1,  

Transcription & Epigenetics ⓘ

other↝, 1,   PhotoS↑, 1,   tumCV↓, 5,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   eIF2α↑, 1,   p‑eIF2α↑, 1,   ER Stress↑, 4,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   HSP90↓, 2,   IRE1↑, 1,   PERK↑, 2,   UPR↑, 2,   XBP-1↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   LC3A↑, 1,   p62↓, 2,   p62↑, 1,   TumAuto↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 5,   DNMT1↓, 1,   m-FAM72A↓, 1,   P53↓, 2,   P53↑, 2,   PARP↑, 2,   cl‑PARP↑, 4,   PCNA↓, 1,   SIRT6↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 4,   CDK4↓, 1,   Cyc↓, 1,   cycA1/CCNA1↓, 1,   CycB/CCNB1↓, 1,   cycD1/CCND1↓, 5,   CycD3↓, 1,   P21↓, 1,   P21↑, 3,   TumCCA↑, 10,  

Proliferation, Differentiation & Cell State ⓘ

cMYB↓, 1,   CSCs↓, 4,   EMT↓, 11,   ERK↓, 3,   p‑ERK↑, 1,   FOXO3↑, 2,   Gli↓, 1,   Gli1↓, 1,   p‑GSK‐3β↓, 1,   HDAC↓, 3,   HDAC1↓, 1,   HDAC3↓, 1,   HDAC8↓, 1,   IGF-1↓, 2,   Let-7↑, 1,   mTOR↓, 8,   mTOR↑, 1,   p‑mTOR↓, 2,   p‑mTOR↑, 1,   Nanog↓, 1,   NOTCH↓, 1,   NOTCH1↑, 3,   OCT4↓, 2,   P70S6K↑, 1,   PI3K↓, 8,   PI3K↑, 1,   p‑PI3K↓, 1,   PTEN↑, 2,   SCF↓, 1,   Shh↓, 1,   SHP1↑, 1,   Smo↓, 1,   SOX2↓, 1,   STAT3↓, 14,   p‑STAT3↓, 2,   TOP1↓, 2,   TOP2↓, 1,   TumCG↓, 6,   Wnt↓, 2,  

Migration ⓘ

annexin II↓, 1,   AP-1↓, 1,   Ca+2↑, 5,   CAFs/TAFs↓, 1,   CLDN1↓, 1,   E-cadherin↑, 7,   FAK↓, 2,   p‑FAK↓, 1,   Fibronectin↓, 1,   Ki-67↓, 1,   MMP-10↓, 1,   MMP2↓, 7,   MMP9↓, 7,   MMP9↑, 1,   MMPs↓, 1,   N-cadherin↓, 3,   Rho↓, 1,   ROCK1↓, 5,   Slug↓, 1,   Smad1↑, 1,   Snail↓, 4,   TET1↑, 2,   TGF-β↑, 1,   TIMP1↓, 1,   TIMP2↓, 1,   TumCI↓, 10,   TumCMig↓, 9,   TumCP↓, 13,   TumCP↑, 1,   TumMeta↓, 8,   TumMeta↑, 1,   Twist↓, 4,   uPA↓, 3,   Vim↓, 7,   ZO-1↑, 1,   β-catenin/ZEB1↓, 4,  

Angiogenesis & Vasculature ⓘ

angioG↓, 6,   ATF4↑, 1,   EGFR↓, 6,   Hif1a↓, 11,   VEGF↓, 10,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

BBB↑, 1,   GLUT1↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 4,   COX2↑, 2,   IKKα↓, 1,   IL10↓, 1,   IL1β↓, 3,   IL2↑, 1,   IL6↓, 4,   IL8↓, 1,   JAK↝, 1,   JAK2↓, 1,   NF-kB↓, 9,   NF-kB↑, 1,   NF-kB↝, 1,   p65↓, 2,   p‑p65↓, 1,   PD-L1↓, 2,   PGE2↓, 1,   TLR4↓, 1,   TNF-α↓, 2,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 2,   CDK6↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 3,   BioEnh↑, 1,   ChemoSen↑, 21,   Dose∅, 2,   eff↓, 2,   eff↑, 19,   eff↝, 2,   Half-Life↓, 1,   MRP1↓, 2,   RadioS↑, 6,   selectivity↑, 5,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   ALP↓, 1,   AR↓, 2,   EGFR↓, 6,   Ferritin↑, 1,   GutMicro↑, 1,   HER2/EBBR2↓, 1,   hTERT/TERT↓, 2,   IL6↓, 4,   Ki-67↓, 1,   LDH↓, 1,   PD-L1↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 6,   cardioP↑, 1,   chemoP↑, 1,   chemoPv↑, 3,   neuroP↑, 1,   OS↑, 2,   QoL↑, 1,   RenoP↑, 2,   Risk↓, 1,   toxicity↓, 1,   toxicity↝, 2,   TumVol↓, 1,  
Total Targets: 272

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx?, 1,   antiOx↑, 3,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   HO-1↑, 1,   MDA↓, 1,   NRF2↓, 1,   ROS↓, 3,   SOD↑, 1,  

Core Metabolism/Glycolysis ⓘ

lipidLev↓, 1,   NADPH↑, 1,  

Cell Death ⓘ

Akt↓, 1,   Casp3∅, 1,   Casp9∅, 1,   Cyt‑c∅, 1,   iNOS↓, 1,   iNOS↑, 1,   JNK↓, 1,   MAPK↓, 1,  

DNA Damage & Repair ⓘ

DNArepair↑, 1,   PARP∅, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   PI3K↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL2↓, 1,   IL6↓, 1,   Inflam↓, 5,   NF-kB↓, 3,   TNF-α↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,  

Clinical Biomarkers ⓘ

AST↓, 1,   IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   cognitive↑, 1,   hepatoP↑, 2,   neuroP↑, 2,   RenoP↑, 1,   toxicity↓, 2,  
Total Targets: 40

Scientific Paper Hit Count for: NRF2, nuclear factor erythroid 2-related factor 2
14 brusatol
10 Luteolin
7 Chrysin
6 Apigenin (mainly Parsley)
6 Quercetin
5 Shikonin
4 Vitamin C (Ascorbic Acid)
4 Selenium
3 doxorubicin
3 Ashwagandha(Withaferin A)
3 Baicalein
3 Berberine
3 Brucea javanica
3 Disulfiram
3 Copper and Cu NanoParticles
3 Fisetin
2 Silver-NanoParticles
2 Alpha-Lipoic-Acid
2 Artemisinin
2 Berbamine
2 Propolis -bee glue
2 Chemotherapy
2 Lycopene
2 Pterostilbene
2 salinomycin
2 Radiotherapy/Radiation
2 Selenium NanoParticles
2 Selenite (Sodium)
2 Thymoquinone
1 Allicin (mainly Garlic)
1 Docetaxel
1 Cisplatin
1 Lapatinib
1 Betulinic acid
1 Boron
1 Curcumin
1 diet FMD Fasting Mimicking Diet
1 Ellagic acid
1 EGCG (Epigallocatechin Gallate)
1 HydroxyTyrosol
1 Juglone
1 Metformin
1 Mushroom Lion’s Mane
1 Myricetin
1 Propyl gallate
1 Piperlongumine
1 Plumbagin
1 Resveratrol
1 Sulfasalazine
1 Oxygen, Hyperbaric
1 irinotecan
1 triptolide
1 xanthohumol
1 Phenethyl isothiocyanate
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#:226  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

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