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

Stroke, Cerebral Ischemic Stroke: Click to Expand ⟱
Ischemic stroke is also called brain ischemia and cerebral ischemia. Ischemia is the medical term for "lack of blood supply."

Quick Reference

Mechanism Top Compounds
Blood flow / anti-thrombotic support Aspirin, Ginkgo biloba, Panax notoginseng, Salvia miltiorrhiza
Membrane repair / cholinergic support Citicoline, Alpha-GPC
Antioxidant / ROS control EGCG, Curcumin, Quercetin, Tocotrienols
Anti-inflammatory / NF-κB / cytokines Curcumin, Luteolin, Baicalin
Mitochondrial protection Resveratrol, Citicoline
BBB protection Rosmarinic acid, Astragaloside IV

Stroke/Product Table - Dose + Practical Therapeutic Index

Compound Class Primary Mechanisms Key Stroke Effects Evidence Level Phase Utility Human Dose Range Approx. HED mg/kg/day Practical Therapeutic Index
Aspirin NSAID / anti-platelet COX-1 inhibition; ↓ thromboxane A2; ↓ platelet aggregation Reduces recurrent ischemic stroke risk Strong clinical; standard of care Acute + prevention 81–325 mg/day ~1.2–4.6 mg/kg/day for 70 kg adult High, but bleeding-risk limited
Citicoline / CDP-choline Choline donor Membrane repair; ↑ phosphatidylcholine; ↓ free fatty acid release May support neurological and cognitive recovery Clinical; mixed acute results, better recovery/cognition signal Recovery 500–2000 mg/day ~7–29 mg/kg/day for 70 kg adult Moderate–High
Alpha-GPC Choline donor ↑ acetylcholine; phospholipid support May support post-stroke cognition Clinical; moderate support Recovery 300–1200 mg/day ~4–17 mg/kg/day for 70 kg adult Moderate; TMAO concern
Ginkgo biloba Herbal extract Cerebral blood flow; antioxidant; anti-platelet May support perfusion and cognition Clinical + preclinical Recovery 120–240 mg/day standardized extract ~1.7–3.4 mg/kg/day Moderate; bleeding interaction caution
Panax notoginseng / PNS Saponins Anti-thrombotic; perfusion; anti-inflammatory Improved blood flow/recovery measures in some studies Clinical mainly China + preclinical Acute + recovery Variable extract-dependent Study-specific; often preclinical HED needed Moderate; bleeding interaction caution
Salvia miltiorrhiza / Danshen Herbal extract Microcirculation; vascular protection; anti-platelet May support vascular recovery Clinical mainly China + preclinical Acute + recovery Variable extract/root equivalent Study-specific Moderate; bleeding interaction caution
Baicalin Flavonoid Anti-inflammatory; anti-apoptotic; antioxidant Neuroprotection in ischemic injury models Preclinical + limited clinical Acute No established stroke dose Preclinical HED only Moderate–Low
Curcumin Polyphenol ↓ NF-κB; ↓ cytokines; antioxidant Reduced infarct size/inflammation in models Strong preclinical Acute + recovery 500–2000 mg/day bioavailable form ~7–29 mg/kg/day Moderate; bioavailability limited
Resveratrol Polyphenol SIRT1; mitochondrial protection; anti-apoptotic Reduced apoptosis/infarct injury in models Strong preclinical Acute + recovery 100–500 mg/day ~1.4–7.1 mg/kg/day Moderate; bioavailability limited
EGCG Catechin ROS scavenging; vascular protection Reduced neuronal injury in models Strong preclinical Acute 200–400 mg/day EGCG ~2.9–5.7 mg/kg/day Moderate; liver-dose caution
Quercetin Flavonoid Antioxidant; anti-inflammatory; anti-edema Reduced edema/infarct size in models Strong preclinical Acute 500–1000 mg/day ~7–14 mg/kg/day Moderate
Melatonin Indoleamine Mitochondrial antioxidant; anti-inflammatory Reduced ischemia-reperfusion injury in models Preclinical + limited clinical interest Acute + recovery 3–10 mg/day ~0.04–0.14 mg/kg/day Moderate–High
Tocotrienols Vitamin E subtype Lipid antioxidant; membrane protection Neuroprotection in ischemic models Preclinical + limited clinical Acute 100–300 mg/day ~1.4–4.3 mg/kg/day Moderate
Luteolin Flavonoid NF-κB / Nrf2 / PI3K-Akt modulation Reduced inflammation/neuroprotection in models Strong preclinical Acute No established stroke dose Preclinical HED only Low–Moderate
Ferulic acid Phenolic acid Antioxidant; vasodilation; vascular protection Improved blood flow/reduced injury in models Preclinical Acute No established stroke dose Preclinical HED only Low–Moderate
Rosmarinic acid Phenolic acid BBB protection; antioxidant; anti-inflammatory Reduced BBB disruption in models Preclinical Acute No established stroke dose Preclinical HED only Low–Moderate
Berberine Alkaloid AMPK activation; metabolic/vascular protection Neuroprotection in ischemia models Preclinical Prevention + recovery 500–1500 mg/day ~7–21 mg/kg/day Moderate; interaction caution
Huperzine A Alkaloid AChE inhibition; cholinergic support May support cognitive recovery Preclinical + cognitive clinical context Recovery 100–200 µg/day ~0.001–0.003 mg/kg/day Low–Moderate; narrow cholinergic tolerance
Honokiol Lignan Mitochondrial protection; anti-inflammatory Reduced ischemic neuronal injury in models Preclinical Acute + recovery No established stroke dose Preclinical HED only Low
HED: Human Equilvalent Dose
Scientific Papers found: Click to Expand⟱
2625- Ba,  LT,    Baicalein and luteolin inhibit ischemia/reperfusion-induced ferroptosis in rat cardiomyocyte
- in-vivo, Stroke, NA
*lipid-P↓, *ACSL4∅, *NRF2∅, *GPx4∅, *Ferroptosis↓, *ROS↓, *MDA↓, *eff↑, *HO-1∅,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

Ferroptosis↓, 1,   GPx4∅, 1,   HO-1∅, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2∅, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACSL4∅, 1,  

Cell Death ⓘ

Ferroptosis↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  
Total Targets: 10

Scientific Paper Hit Count for: NRF2, nuclear factor erythroid 2-related factor 2
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:36  Cells:%  prod#:%  Target#:226  State#:%  Dir#:6
  wNotes=0  sortOrder:rid,rpid

 

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