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

BC, Breast Cancer: Click to Expand ⟱
Breast Cancer
Scientific Papers found: Click to Expand⟱
3388- ART/DHA,    Keap1 Cystenine 151 as a Potential Target for Artemisitene-Induced Nrf2 Activation
- in-vitro, Lung, A549 - in-vitro, Nor, GP-293 - in-vitro, BC, MDA-MB-231
NRF2↑, ROS∅,
1385- BBR,  5-FU,    Low-Dose Berberine Attenuates the Anti-Breast Cancer Activity of Chemotherapeutic Agents via Induction of Autophagy and Antioxidation
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
eff↓, ROS↑, TumCP↑, NRF2↑, ChemoSen↓,
13- CUR,    Role of curcumin in regulating p53 in breast cancer: an overview of the mechanism of action
- Review, BC, NA
P53↑, DR5↑, JNK↑, NRF2↑, PPARγ↑, HER2/EBBR2↓, IR↓, ER(estro)↓, Fas↑, PDGF↓, TGF-β↓, FGF↓, EGFR↓, JAK↓, PAK↓, MAPK↓, ATPase↓, COX2↓, MMPs↓, IL1↓, IL2↓, IL5↓, IL6↓, IL8↓, IL12↓, IL18↓, NF-kB↓, NOTCH1↓, STAT1↓, STAT4↓, STAT5↓, STAT3↓,
414- CUR,    Transcriptome Investigation and In Vitro Verification of Curcumin-Induced HO-1 as a Feature of Ferroptosis in Breast Cancer Cells
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
Ferroptosis↑, Iron↑, ROS↑, lipid-P↑, MDA↑, GSH↓, HO-1↑, NRF2↑, GPx↓, ROS↑, Iron↑, GPx4↓, HSP70/HSPA5↑, ATFs↑, CHOP↑, MDA↑, FTL↑, FTH1↑, BACH1↑, REL↑, USF1↑, NFE2L2↑,
3214- EGCG,    EGCG-induced selective death of cancer cells through autophagy-dependent regulation of the p62-mediated antioxidant survival pathway
- in-vitro, Nor, MRC-5 - in-vitro, Cerv, HeLa - in-vitro, Nor, HEK293 - in-vitro, BC, MDA-MB-231 - in-vitro, CRC, HCT116
mTOR↓, AMPK↑, selectivity↑, ROS↑, selectivity↑, HO-1↓, *NRF2↑, NRF2↓, *HO-1↑,
2858- FIS,    Fisetin inhibits cell migration via inducing HO-1 and reducing MMPs expression in breast cancer cell lines
- in-vitro, BC, 4T1
HO-1↑, NRF2↑, MMP2↓, MMP9↓,
2833- FIS,  AgNPs,    Glucose-capped fisetin silver nanoparticles induced cytotoxicity and ferroptosis in breast cancer cells: A molecular perspective
- in-vitro, BC, MDA-MB-231
MMP↓, ROS↑, NRF2↑, NOX↑, selectivity↑,
2521- H2,    Oxyhydrogen Gas: A Promising Therapeutic Approach for Lung, Breast and Colorectal Cancer
- Review, CRC, NA - Review, Lung, NA - Review, BC, NA
Inflam↑, ROS↓, ChemoSen↑, p‑PI3K↓, p‑Akt↓, QoL↑, GutMicro↑, chemoP↑, radioP↑, *NRF2↑, *Catalase↑, *GPx↑, *HO-1↑, *SOD↑, *TNF-α↓, *IL4↓, *IL6↓, ChemoSen↑, Appetite↑, cognitive↑, Pain↓, Sleep↑, other?,
4941- PEITC,    PEITC: A resounding molecule averts metastasis in breast cancer cells in vitro by regulating PKCδ/Aurora A interplay
- in-vitro, BC, MCF-7 - in-vitro, BC, MDA-MB-231
PKCδ↑, Apoptosis↓, selectivity↑, tumCV↓, p‑NRF2↑, cl‑PARP1↑, TumCMig↓, ROS↓, Hif1a↓,
2955- PL,    Heme Oxygenase-1 Determines the Differential Response of Breast Cancer and Normal Cells to Piperlongumine
- in-vitro, BC, MCF-7 - in-vitro, Nor, MCF10
ROS?, *ROS∅, other⇅, HO-1↑, *HO-1↑, NRF2↑, Keap1↓, cl‑PARP↑, selectivity↑, GSH↓, GSSG↑,
3092- RES,    Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action
- Review, BC, MDA-MB-231 - Review, BC, MCF-7
TumCP↓, tumCV↓, TumCI↓, TumMeta↓, *antiOx↑, *cardioP↑, *Inflam↓, *neuroP↑, *Keap1↓, *NRF2↑, *ROS↓, p62↓, IL1β↓, CRP↓, VEGF↓, Bcl-2↓, MMP2↓, MMP9↓, FOXO4↓, POLD1↓, CK2↓, MMP↓, ROS↑, Apoptosis↑, TumCCA↑, Beclin-1↓, Ki-67↓, ATP↓, GlutMet↓, PFK↓, TGF-β↓, SMAD2↓, SMAD3↓, Vim?, Snail↓, Slug↓, E-cadherin↑, EMT↓, Zeb1↓, Fibronectin↓, IGF-1↓, PI3K↓, Akt↓, HO-1↑, eff↑, PD-1↓, CD8+↑, Th1 response↑, CSCs↓, RadioS↑, SIRT1↑, Hif1a↓, mTOR↓,
1494- SFN,  doxoR,    Sulforaphane potentiates anticancer effects of doxorubicin and attenuates its cardiotoxicity in a breast cancer model
- in-vivo, BC, NA - in-vitro, BC, MCF-7 - in-vitro, Nor, MCF10
CardioT↓, *GSH↑, *ROS↓, *NRF2↑, NRF2∅, HDAC↓, DNMTs↓, Casp3↑, ER-α36↓, Remission↑, eff↑, ROS↑, selectivity?,
5096- SSE,    Selenium Toxicity Accelerated by Out-of-Control Response of Nrf2-xCT Pathway
- in-vitro, BC, MCF-7
xCT↑, ROS↑, NRF2↑,
1052- TQ,    Thymoquinone Anticancer Effects Through the Upregulation of NRF2 and the Downregulation of PD-L1 in MDA-MB-231 Triple-Negative Breast Cancer Cells
- in-vitro, BC, MDA-MB-231
NRF2↑, PD-L1↓, Apoptosis↑,
4538- TQ,    NRF2_and_the_Downregulation_of_PD-L1_in_MDA-MB-231_Triple-Negative_Breast_Cancer_Cells">Thymoquinone Anticancer Effects Through the Upregulation of NRF2 and the Downregulation of PD‐L1 in MDA‐MB‐231 Triple‐Negative Breast Cancer Cells
- in-vitro, BC, MDA-MB-231 - in-vitro, BC, MDA-MB-468
antiOx↑, H2O2↓, Catalase↑, SOD↑, GSH↑, PRNP↑, NQO1↑, GCLM↑, NRF2↑, PD-L1↓, chemoPv↑, ROS↓,
3399- TQ,    Anticancer Effects of Thymoquinone through the Antioxidant Activity, Upregulation of Nrf2, and Downregulation of PD-L1 in Triple-Negative Breast Cancer Cells
- in-vitro, BC, MDA-MB-231 - NA, BC, MDA-MB-468
ROS↓, H2O2↓, Catalase↑, SOD↑, GSH↑, NQO1↑, GCLM↑, NRF2↑, PD-L1↓, GSSG↑, GPx1⇅, GPx4↓,

Showing Research Papers: 1 to 16 of 16

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 16

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 2,   Ferroptosis↑, 1,   GCLM↑, 2,   GPx↓, 1,   GPx1⇅, 1,   GPx4↓, 2,   GSH↓, 2,   GSH↑, 2,   GSSG↑, 2,   H2O2↓, 2,   HO-1↓, 1,   HO-1↑, 4,   Iron↑, 2,   Keap1↓, 1,   lipid-P↑, 1,   MDA↑, 2,   NFE2L2↑, 1,   NQO1↑, 2,   NRF2↓, 1,   NRF2↑, 11,   NRF2∅, 1,   p‑NRF2↑, 1,   ROS?, 1,   ROS↓, 4,   ROS↑, 8,   ROS∅, 1,   SOD↑, 2,   xCT↑, 1,  

Metal & Cofactor Biology ⓘ

FTH1↑, 1,   FTL↑, 1,  

Mitochondria & Bioenergetics ⓘ

ATP↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   GlutMet↓, 1,   IR↓, 1,   PFK↓, 1,   POLD1↓, 1,   PPARγ↑, 1,   SIRT1↑, 1,  

Cell Death ⓘ

Akt↓, 1,   p‑Akt↓, 1,   Apoptosis↓, 1,   Apoptosis↑, 2,   Bcl-2↓, 1,   Casp3↑, 1,   CK2↓, 1,   DR5↑, 1,   Fas↑, 1,   Ferroptosis↑, 1,   JNK↑, 1,   MAPK↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   PAK↓, 1,  

Transcription & Epigenetics ⓘ

other?, 1,   other⇅, 1,   tumCV↓, 2,   USF1↑, 1,  

Protein Folding & ER Stress ⓘ

ATFs↑, 1,   CHOP↑, 1,   HSP70/HSPA5↑, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↓, 1,   p62↓, 1,  

DNA Damage & Repair ⓘ

DNMTs↓, 1,   P53↑, 1,   cl‑PARP↑, 1,   cl‑PARP1↑, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

CSCs↓, 1,   EMT↓, 1,   FGF↓, 1,   FOXO4↓, 1,   HDAC↓, 1,   IGF-1↓, 1,   mTOR↓, 2,   NOTCH1↓, 1,   PI3K↓, 1,   p‑PI3K↓, 1,   STAT1↓, 1,   STAT3↓, 1,   STAT4↓, 1,   STAT5↓, 1,  

Migration ⓘ

ATPase↓, 1,   BACH1↑, 1,   E-cadherin↑, 1,   ER-α36↓, 1,   Fibronectin↓, 1,   Ki-67↓, 1,   MMP2↓, 2,   MMP9↓, 2,   MMPs↓, 1,   PDGF↓, 1,   PKCδ↑, 1,   PRNP↑, 1,   Slug↓, 1,   SMAD2↓, 1,   SMAD3↓, 1,   Snail↓, 1,   TGF-β↓, 2,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumCP↑, 1,   TumMeta↓, 1,   Vim?, 1,   Zeb1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,   Hif1a↓, 2,   REL↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   CRP↓, 1,   IL1↓, 1,   IL12↓, 1,   IL18↓, 1,   IL1β↓, 1,   IL2↓, 1,   IL5↓, 1,   IL6↓, 1,   IL8↓, 1,   Inflam↑, 1,   JAK↓, 1,   NF-kB↓, 1,   PD-1↓, 1,   PD-L1↓, 3,   Th1 response↑, 1,  

Cellular Microenvironment ⓘ

NOX↑, 1,  

Hormonal & Nuclear Receptors ⓘ

ER(estro)↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↓, 1,   ChemoSen↑, 2,   eff↓, 1,   eff↑, 2,   RadioS↑, 1,   selectivity?, 1,   selectivity↑, 5,  

Clinical Biomarkers ⓘ

CRP↓, 1,   EGFR↓, 1,   GutMicro↑, 1,   HER2/EBBR2↓, 1,   IL6↓, 1,   Ki-67↓, 1,   PD-L1↓, 3,  

Functional Outcomes ⓘ

Appetite↑, 1,   CardioT↓, 1,   chemoP↑, 1,   chemoPv↑, 1,   cognitive↑, 1,   Pain↓, 1,   QoL↑, 1,   radioP↑, 1,   Remission↑, 1,   Sleep↑, 1,  

Infection & Microbiome ⓘ

CD8+↑, 1,  
Total Targets: 153

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   Catalase↑, 1,   GPx↑, 1,   GSH↑, 1,   HO-1↑, 3,   Keap1↓, 1,   NRF2↑, 4,   ROS↓, 2,   ROS∅, 1,   SOD↑, 1,  

Immune & Inflammatory Signaling ⓘ

IL4↓, 1,   IL6↓, 1,   Inflam↓, 1,   TNF-α↓, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   neuroP↑, 1,  
Total Targets: 17

Scientific Paper Hit Count for: NRF2, nuclear factor erythroid 2-related factor 2
3 Thymoquinone
2 Curcumin
2 Fisetin
1 Artemisinin
1 Berberine
1 5-fluorouracil
1 EGCG (Epigallocatechin Gallate)
1 Silver-NanoParticles
1 Hydrogen Gas
1 Phenethyl isothiocyanate
1 Piperlongumine
1 Resveratrol
1 Sulforaphane (mainly Broccoli)
1 doxorubicin
1 Selenite (Sodium)
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:4  Cells:%  prod#:%  Target#:226  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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