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

Lung, Lung Cancer: Click to Expand ⟱
Lung CSC (Cancer Stem Cells) markers (CD133, CD44, ALDHA1, Nanog and Oct4)
Scientific Papers found: Click to Expand⟱
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↑, PDK1↓, NRF2↓, PDK1↓, Bcl-2↓, Casp9↑, Dose∅,
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↓, ChemoSen↑,
5695- BRU,    Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism
- in-vitro, Lung, A549
NRF2↓, ChemoSen↑, Apoptosis↑, TumCP↓, TumCG↓, MRP1↓, GSH↓, cMyc↓,
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↓, TumCMig↓, TumCI↓, Apoptosis↑, EGFR↓, β-catenin/ZEB1↓, Akt↓, STAT3↓, TumMeta↓, ChemoSen↑, NRF2↓, Akt↓, mTOR↓,
5694- BRU,    Brusatol overcomes chemoresistance through inhibition of protein translation
- in-vitro, Lung, A549
NRF2↓, P53↓, P21↓,
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↓, ChemoSen↑, NRF2↓, STAT3↓, PI3K↓, Akt↓, mTOR↓, ROCK1↓, Hif1a↓,
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↓, RadioS↑, DNAdam↑, ROS↑,
2587- LT,    Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs
- in-vitro, Lung, A549
NRF2↓, GSH↓, ChemoSen↑, HO-1↓,
1204- MET,    Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer
- in-vitro, Lung, A549 - in-vitro, Lung, H1299
MDA↑, ROS↑, Iron↑, GSH↓, T-SOD↓, Catalase↓, GPx4↓, xCT↓, NRF2↓, HO-1↓,
4725- Se,    Targeting the Nrf2-Prx1 Pathway with Selenium to Enhance the Efficacy and Selectivity of Cancer Therapy
- in-vitro, Lung, A549 - in-vitro, CRC, HT29
AntiCan↑, NRF2↓, Prx↓, ChemoSen↑, *Prx↑, *NRF2↑,
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↑,
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⇅,

Showing Research Papers: 1 to 12 of 12

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 12

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   ARE/EpRE↑, 1,   Catalase↓, 1,   GPx4↓, 1,   GSH↓, 3,   HO-1↓, 3,   Iron↑, 1,   MDA↑, 1,   NRF2↓, 12,   NRF2⇅, 1,   Prx↓, 1,   ROS↓, 1,   ROS↑, 4,   T-SOD↓, 1,   xCT↓, 1,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   PDK1↓, 2,  

Cell Death ⓘ

Akt↓, 3,   Apoptosis↑, 3,   Bcl-2↓, 1,   Casp9↑, 1,  

Transcription & Epigenetics ⓘ

tumCV↓, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 1,   P53↓, 1,   PARP↓, 1,  

Cell Cycle & Senescence ⓘ

cycA1/CCNA1↓, 1,   CycB/CCNB1↑, 1,   CycD3↑, 1,   cycE/CCNE↓, 1,   P21↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

cDC2↓, 1,   mTOR↓, 2,   PI3K↓, 1,   STAT3↓, 2,   TumCG↓, 1,  

Migration ⓘ

ROCK1↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 2,   Hif1a↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 6,   Dose∅, 1,   eff↑, 1,   MRP1↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 2,  

Functional Outcomes ⓘ

AntiCan↑, 1,  
Total Targets: 51

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

NRF2↑, 1,   Prx↑, 1,  
Total Targets: 2

Scientific Paper Hit Count for: NRF2, nuclear factor erythroid 2-related factor 2
5 brusatol
1 Alpha-Lipoic-Acid
1 Apigenin (mainly Parsley)
1 Docetaxel
1 Brucea javanica
1 Luteolin
1 Metformin
1 Selenium
1 Thymoquinone
1 Vitamin C (Ascorbic Acid)
1 Quercetin
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:15  Cells:%  prod#:%  Target#:226  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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