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⟱
3415- TQ,    The anti-neoplastic impact of thymoquinone from Nigella sativa on small cell lung cancer: In vitro and in vivo investigations
- in-vitro, Lung, H446
tumCV↓, TumCCA↑, ROS↓, CycB/CCNB1↑, CycD3↑, cycA1/CCNA1↓, cycE/CCNE↓, cDC2↓, antiOx↑, PARP↓, NRF2↓, ARE/EpRE↑, eff↑,
3559- TQ,    Molecular signaling pathway targeted therapeutic potential of thymoquinone in Alzheimer’s disease
- Review, AD, NA - Review, Var, NA
*antiOx↑, *Inflam↓, *AChE↓, AntiCan↑, *cardioP↑, *RenoP↑, *neuroP↑, *hepatoP↑, TumCG↓, Apoptosis↑, PI3K↓, Akt↑, TumCCA↑, angioG↓, *NF-kB↓, *TLR2↓, *TLR4↓, *MyD88↓, *TRIF↓, *IRF3↓, *IL1β↓, *IL6↓, *IL12↓, *NRF2↑, *COX2↓, *VEGF↓, *MMP9↓, *cMyc↓, *cycD1/CCND1↓, *TumCP↓, *TumCI↓, *MDA↓, *TGF-β↓, *CRP↓, *Casp3↓, *GSH↑, *IL10↑, *iNOS↑, *lipid-P↓, *SOD↑, *H2O2↓, *ROS↓, *LDH↓, *Catalase↑, *GPx↑, *AChE↓, *cognitive↑, *MAPK↑, *JNK↑, *BAX↓, *memory↑, *Aβ↓, *MMP↑,
2454- Trip,    Natural product triptolide induces GSDME-mediated pyroptosis in head and neck cancer through suppressing mitochondrial hexokinase-ΙΙ
- in-vitro, HNSCC, HaCaT - in-vivo, NA, NA
GSDME-N↑, Pyro↑, cMyc↓, HK2↓, BAD↑, BAX↑, Casp3↑, NRF2↓, xCT↓, ROS↑, eff↑, Glycolysis↓, GlucoseCon↓, lactateProd↓, ATP↓, xCT↓, eff↑,
5934- TV,    Protective Effects of Natural Antioxidants on Inflammatory Bowel Disease: Thymol and Its Pharmacological Properties
- Review, Var, NA
*Inflam↓, *antiOx↑, *Bacteria↓, AntiTum↑, *toxicity∅, *IBI↑, *ZO-1↑, *OCLN↑, *COX1↑, *TLR4↓, *NF-kB↓, *TNF-α↓, *IL1β↓, *TAC↑, *NRF2↑, *GutMicro↑,
4869- Uro,    Urolithin A in Central Nervous System Disorders: Therapeutic Applications and Challenges
- Review, AD, NA - Review, Park, NA - Review, Stroke, NA
*MitoP↑, *Inflam↓, *antiOx↑, *Risk↓, *Aβ↓, *p‑tau↓, *p62↓, *PARK2↑, *MMP↑, *ROS↓, *Strength↑, *CRP↓, *IL1β↓, *IL6↓, *TNF-α↓, *AMPK↑, *NF-kB↓, *MAPK↓, *p62↑, *NRF2↑, *SOD↑, *Catalase↑, *HO-1↑, *Ferroptosis↓, *lipid-P↓, *Cartilage↑, *PI3K↓, *Akt↓, *mTOR↓, *Apoptosis↓, *neuroP↑, *Bcl-2↓, *BAX↑, *Casp3↑, *ATP↑, *eff↑, *motorD↑, *NLRP3↓, *radioP↑, *BBB↑,
4875- Uro,    Impact of the Natural Compound Urolithin A on Health, Disease, and Aging
- Review, AD, NA - Review, Stroke, NA - Review, ostP, NA - Review, IBD, NA
*MitoP↓, *Strength↑, *PINK1↑, *PARK2↑, *Inflam↓, *COX2↓, *IL1β↓, *IL6↓, *TNF-α↓, *OS↑, *cardioP↑, *memory↑, *neuroG↑, *neuroP↑, *Cartilage↑, *Inflam↓, *RenoP↑, *eff↑, *Dose↝, *Half-Life↑, *NRF2↑, *GutMicro↑,
4876- Uro,    Urolithin A in Health and Diseases: Prospects for Parkinson’s Disease Management
- Review, Park, NA - Review, AD, NA
*Inflam↓, *antiOx↓, *neuroP↑, *p‑tau↓, *Aβ↓, *eff↑, *BioAv↓, *BioAv↑, *GSH↑, *SOD↑, *lipid-P↓, *Catalase↑, *GSR↑, *GPx↑, *ROS↓, *NRF2↑, *GutMicro↑, *Risk↓, *BBB↓, *NLRP3↓, *MAOA↓,
4877- Uro,    Urolithin-A Derivative UAS03 Improves Cognitive Deficits and Memory by Activating Nrf2 Pathways to Alleviate Oxidative Stress and Neuroinflammation
- in-vivo, AD, NA
*cognitive↑, *memory↑, *neuroP↑, *NRF2↑, *ROS↓, *Inflam↓, *IL1β↓, *TNF-α↓, *COX2↓,
4311- VitB1/Thiamine,    Benfotiamine treatment activates the Nrf2/ARE pathway and is neuroprotective in a transgenic mouse model of tauopathy
- in-vivo, AD, NA
*Aβ↓, *p‑tau↓, *ROS↓, *cognitive↑, *OS↑, *Mood↑, *neuroP↑, *Inflam↓, *NRF2↑, *PGC-1α↑, *AGEs↓, *4-HNE↓, *NQO1↑, *COX2↓, *TNF-α↓, *IL1β↓, *NF-kB↓, *GSK‐3β↓,
114- VitC,  QC,    Chemoprevention of prostate cancer cells by vitamin C plus quercetin: role of Nrf2 in inducing oxidative stress
- in-vitro, Pca, PC3 - in-vitro, Pca, DU145
GPx↓, GSR↓, NQO1↓, NRF2↓, ROS↑,
2592- VitC,    Ascorbic acid restores sensitivity to imatinib via suppression of Nrf2-dependent gene expression in the imatinib-resistant cell line
- in-vitro, CLL, NA
NRF2↓, GSH↓,
3108- VitC,  QC,    The role of quercetin and vitamin C in Nrf2-dependent oxidative stress production in breast cancer cells
- in-vitro, BC, MDA-MB-231 - in-vitro, Lung, A549
NRF2↓, HO-1↓, ROS↑, NRF2⇅,
3109- VitC,    Vitamin C Inhibited Pulmonary Metastasis through Activating Nrf2/HO-1 Pathway
- in-vitro, Lung, H1299
TumMeta↓, NRF2↑, HO-1↑, cl‑Casp3↑, cl‑Casp9↑, DNAdam↑, Apoptosis↑, other↑, selectivity↑,
3110- VitC,    Vitamin C Attenuates Oxidative Stress, Inflammation, and Apoptosis Induced by Acute Hypoxia through the Nrf2/Keap1 Signaling Pathway in Gibel Carp (Carassius gibelio)
- in-vivo, Nor, NA
*IL2↑, *IL6↑, *IL12↑, *NRF2↑, *Catalase↑, *SOD↑, *GPx↑, *GRP78/BiP↓, *ER Stress↓,
3112- VitC,    Antioxidative and Anti-Inflammatory Activity of Ascorbic Acid
- Review, Nor, NA
*ROS↓, *antiOx↑, *SOD↑, *Catalase↑, *GPx↑, *NRF2↑, *AP-1↑, *Inflam↓, *CRP↓, IFN-γ↓,
1741- VitD3,    Vitamin D Deficiency: Effects on Oxidative Stress, Epigenetics, Gene Regulation, and Aging
- Review, Var, NA
*Inflam↓, *antiOx↑, *eff↑, *ROS↓, *NRF2↑, *GPx↑, *Dose↝, Dose↑,
2276- VitK2,    Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat
- in-vivo, Nor, NA
*Albumin↑, *AST↓, *ALAT↓, *Keap1↓, *NRF2↑, *HO-1↑, *COX2↓, *iNOS↓, *TNF-α↓, *TIMP1↓, *TGF-β↓, *ROS↓, *DNAdam↓, *Inflam↓,
5015- Xan,  PEITC,    Comparison of the Impact of Xanthohumol and Phenethyl Isothiocyanate and Their Combination on Nrf2 and NF-κB Pathways in HepG2 Cells In Vitro and Tumor Burden In Vivo
- in-vitro, HCC, HepG2
NRF2↓, ROS↑, NF-kB↓, COX2↓, Apoptosis↑, NRF2↑, SOD↑, NQO1↑,

Showing Research Papers: 451 to 468 of 468
Prev Page 10 of 10

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 468

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ARE/EpRE↑, 1,   GPx↓, 1,   GSH↓, 1,   GSR↓, 1,   HO-1↓, 1,   HO-1↑, 1,   NQO1↓, 1,   NQO1↑, 1,   NRF2↓, 6,   NRF2↑, 2,   NRF2⇅, 1,   ROS↓, 1,   ROS↑, 4,   SOD↑, 1,   xCT↓, 2,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   GlucoseCon↓, 1,   Glycolysis↓, 1,   HK2↓, 1,   lactateProd↓, 1,  

Cell Death ⓘ

Akt↑, 1,   Apoptosis↑, 3,   BAD↑, 1,   BAX↑, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   cl‑Casp9↑, 1,   GSDME-N↑, 1,   Pyro↑, 1,  

Transcription & Epigenetics ⓘ

other↑, 1,   tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   PARP↓, 1,  

Cell Cycle & Senescence ⓘ

cycA1/CCNA1↓, 1,   CycB/CCNB1↑, 1,   CycD3↑, 1,   cycE/CCNE↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

cDC2↓, 1,   PI3K↓, 1,   TumCG↓, 1,  

Migration ⓘ

TumMeta↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IFN-γ↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

Dose↑, 1,   eff↑, 3,   selectivity↑, 1,  

Functional Outcomes ⓘ

AntiCan↑, 1,   AntiTum↑, 1,  
Total Targets: 53

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

4-HNE↓, 1,   antiOx↓, 1,   antiOx↑, 5,   Catalase↑, 5,   Ferroptosis↓, 1,   GPx↑, 5,   GSH↑, 2,   GSR↑, 1,   H2O2↓, 1,   HO-1↑, 2,   Keap1↓, 1,   lipid-P↓, 3,   MDA↓, 1,   NQO1↑, 1,   NRF2↑, 11,   PARK2↑, 2,   ROS↓, 8,   SOD↑, 5,   TAC↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↑, 1,   MMP↑, 2,   PGC-1α↑, 1,   PINK1↑, 1,  

Core Metabolism/Glycolysis ⓘ

ALAT↓, 1,   AMPK↑, 1,   cMyc↓, 1,   LDH↓, 1,  

Cell Death ⓘ

Akt↓, 1,   Apoptosis↓, 1,   BAX↓, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp3↓, 1,   Casp3↑, 1,   Ferroptosis↓, 1,   iNOS↓, 1,   iNOS↑, 1,   JNK↑, 1,   MAPK↓, 1,   MAPK↑, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↓, 1,   GRP78/BiP↓, 1,  

Autophagy & Lysosomes ⓘ

MitoP↓, 1,   MitoP↑, 1,   p62↓, 1,   p62↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↓, 1,  

Cell Cycle & Senescence ⓘ

cycD1/CCND1↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

GSK‐3β↓, 1,   mTOR↓, 1,   neuroG↑, 1,   PI3K↓, 1,  

Migration ⓘ

AP-1↑, 1,   Cartilage↑, 2,   MMP9↓, 1,   TGF-β↓, 2,   TIMP1↓, 1,   TumCI↓, 1,   TumCP↓, 1,   ZO-1↑, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Barriers & Transport ⓘ

BBB↓, 1,   BBB↑, 1,   IBI↑, 1,   OCLN↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX1↑, 1,   COX2↓, 5,   CRP↓, 3,   IL10↑, 1,   IL12↓, 1,   IL12↑, 1,   IL1β↓, 6,   IL2↑, 1,   IL6↓, 3,   IL6↑, 1,   Inflam↓, 11,   MyD88↓, 1,   NF-kB↓, 4,   TLR2↓, 1,   TLR4↓, 2,   TNF-α↓, 6,   TRIF↓, 1,  

Synaptic & Neurotransmission ⓘ

AChE↓, 2,   MAOA↓, 1,   p‑tau↓, 3,  

Protein Aggregation ⓘ

AGEs↓, 1,   Aβ↓, 4,   NLRP3↓, 2,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   BioAv↑, 1,   Dose↝, 2,   eff↑, 4,   Half-Life↑, 1,  

Clinical Biomarkers ⓘ

ALAT↓, 1,   Albumin↑, 1,   AST↓, 1,   CRP↓, 3,   GutMicro↑, 3,   IL6↓, 3,   IL6↑, 1,   LDH↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 2,   cognitive↑, 3,   hepatoP↑, 1,   memory↑, 3,   Mood↑, 1,   motorD↑, 1,   neuroP↑, 6,   OS↑, 2,   radioP↑, 1,   RenoP↑, 2,   Risk↓, 2,   Strength↑, 2,   toxicity∅, 1,  

Infection & Microbiome ⓘ

Bacteria↓, 1,   IRF3↓, 1,  
Total Targets: 116

Scientific Paper Hit Count for: NRF2, nuclear factor erythroid 2-related factor 2
38 Sulforaphane (mainly Broccoli)
23 Thymoquinone
22 Quercetin
20 Curcumin
18 Resveratrol
16 EGCG (Epigallocatechin Gallate)
16 Lycopene
15 Shikonin
14 Luteolin
14 brusatol
13 Silymarin (Milk Thistle) silibinin
12 Alpha-Lipoic-Acid
12 Baicalein
11 Ashwagandha(Withaferin A)
11 Fisetin
10 doxorubicin
10 Apigenin (mainly Parsley)
10 Chemotherapy
9 Silver-NanoParticles
9 Selenite (Sodium)
9 Artemisinin
9 Selenium
9 Chrysin
8 Vitamin C (Ascorbic Acid)
8 Boron
8 Chlorogenic acid
8 Propolis -bee glue
8 Hydrogen Gas
8 Pterostilbene
8 Rosmarinic acid
7 Radiotherapy/Radiation
7 Carnosic acid
7 Piperlongumine
6 Allicin (mainly Garlic)
6 Berberine
6 Honokiol
5 Betulinic acid
5 Boswellia (frankincense)
4 Selenium NanoParticles
4 Phenethyl isothiocyanate
4 Urolithin
3 Cisplatin
3 Astaxanthin
3 Berbamine
3 5-fluorouracil
3 Brucea javanica
3 Capsaicin
3 Carvacrol
3 Disulfiram
3 Copper and Cu NanoParticles
3 Magnetic Fields
3 Parthenolide
2 Auranofin
2 Caffeic Acid Phenethyl Ester (CAPE)
2 Thymol-Thymus vulgaris
2 Ferulic acid
2 HydroxyTyrosol
2 Metformin
2 Methylsulfonylmethane
2 xanthohumol
2 salinomycin
2 Taurine
1 Andrographis
1 Docetaxel
1 Baicalin
1 Lapatinib
1 Biochanin A
1 Butyrate
1 Catechins
1 Celastrol
1 chitosan
1 Calorie Restriction Mimetics
1 Ursolic acid
1 Cysteamine
1 diet FMD Fasting Mimicking Diet
1 diet Methionine-Restricted Diet
1 Ellagic acid
1 Emodin
1 Shilajit/Fulvic Acid
1 Ginkgo biloba
1 Ginseng
1 HydroxyCitric Acid
1 Hydroxycinnamic-acid
1 Juglone
1 Magnolol
1 Melatonin
1 Mushroom Lion’s Mane
1 Myricetin
1 Oleuropein
1 Propyl gallate
1 Piperine
1 Plumbagin
1 Sulfasalazine
1 Oxygen, Hyperbaric
1 irinotecan
1 acetazolamide
1 Salvia miltiorrhiza
1 Spermidine
1 erastin
1 triptolide
1 Vitamin B1/Thiamine
1 Vitamin D3
1 Vitamin K2
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#:%
  wNotes=0  sortOrder:rid,rpid

 

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