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

PSA, Psoriasis: Click to Expand ⟱
Psoriasis is an autoimmune skin disease.
This section mainly deals with PsA which is psoriatic arthritis

PsA evidence based approach

Rank Approach Evidence Mechanism / Rationale Notes
1 Weight loss if overweight/obese Best direct evidence in PsA Reduces metabolic inflammation, adipokine burden, and joint inflammatory load; may improve treatment response. Highest-yield natural strategy when excess weight is present.
2 Regular exercise / physical activity Good supportive evidence Improves pain, stiffness, function, fatigue, muscle support, and cardiometabolic health. Strong adjunct for joint symptoms and overall health.
3 Mediterranean-style diet / antioxidant-rich whole-food diet Moderate evidence May reduce systemic inflammatory tone; provides polyphenols, fiber, unsaturated fats, and better metabolic support. Best antioxidant strategy is diet pattern rather than antioxidant pills.
4 Intermittent fasting / time-restricted eating Early limited evidence May improve inflammatory signaling and metabolic regulation; possible benefit for CRP, enthesitis, and disease activity. Promising but still exploratory.
5 Omega-3 (fish / fish oil) Mixed evidence Shifts eicosanoids toward less inflammatory profiles and may modestly reduce inflammatory tone. Reasonable adjunct, but not a top-tier PsA joint intervention.
6 Vitamin D Weak PsA-specific treatment evidence More relevant for deficiency correction, bone support, and immune modulation than for direct joint control. Most relevant when levels are low.

PsA pathways to modulate

Rank Pathway / Axis Why It Matters in PsA Joints Helpful Modulation Support Level
1 IL-23 → Th17/Tc17 → IL-17A/F Core inflammatory axis in psoriatic arthritis; active in synovium, enthesis, and related tissues. Reduce excessive IL-23 / IL-17 signaling and downstream cytokine/chemokine output. Very high
2 TNF-α / NF-κB inflammatory axis Major validated cytokine pathway driving inflammation, tissue injury, and amplification of disease activity. Reduce TNF / NF-κB-driven inflammatory signaling and matrix damage. Very high
3 JAK / STAT3 signaling Supports cytokine signaling relevant to synovial and entheseal inflammation. Dampen excessive JAK / STAT3 inflammatory activity. High
4 Myeloid / inflammasome amplification (IL-1β, IL-6, GM-CSF) Amplifies synovitis, pain, recruitment of inflammatory cells, and osteoclastogenic signaling. Reduce IL-1β, IL-6, and GM-CSF inflammatory amplification. High
5 RANKL / M-CSF / osteoclastogenesis Important for bone erosions and osteoclast-mediated damage. Reduce osteoclast differentiation and bone resorption pressure. High
6 DKK1 / Wnt / BMP bone-remodeling balance PsA involves both erosions and abnormal new bone formation. Rebalance remodeling rather than simply suppress all bone formation. Moderate to high
7 COX-2 / 5-LOX / eicosanoid signaling Contributes to inflammatory pain, swelling, and leukocyte recruitment. Reduce excess prostaglandin and leukotriene inflammatory tone. Moderate
8 KEAP1-NRF2 / oxidative stress-redox balance Oxidative imbalance may reinforce inflammatory signaling and tissue injury. Improve antioxidant defense and redox resilience. Moderate
9 Obesity / adipokine / metabolic inflammation axis Obesity is linked to worse disease activity and poorer response. Reduce metabolic inflammation and adverse adipokine signaling. Moderate
10 Gut microbiome / barrier / immune-metabolite axis Gut dysbiosis and barrier changes may influence systemic immune activation. Support gut barrier function and more favorable immune-metabolic signaling. Moderate

Natural products that might help PsA — mechanistic HTML table

Natural Product / Class Main PsA-Relevant Pathways Mechanistic Rationale Direct PsA Joint Evidence Practical Read
Omega-3 (EPA/DHA) IL-17-related signaling; TNF/NF-κB tone; eicosanoids / resolution pathways May shift lipid mediators toward less inflammatory profiles and reduce inflammatory signaling. Mixed / weak Most practical food/supplement adjunct, but not a strong standalone PsA joint therapy.
Curcumin / Turmeric NF-κB; JAK/STAT3; MAPK; IL-17 / IFN-γ; redox signaling Broad anti-inflammatory and signaling-modulating effects relevant to psoriatic disease biology. Very limited direct evidence Reasonable mechanistic adjunct; stronger biology than clinical PsA proof.
Boswellia / Boswellic acids 5-LOX; NF-κB; COX-2; leukotrienes Notable leukotriene / 5-LOX angle with broader anti-inflammatory effects. No strong direct PsA joint trials Plausible adjunct, especially for eicosanoid-driven inflammation.
Ginger NF-κB; COX / LOX; inflammatory pain pathways Anti-inflammatory and antioxidant actions with arthritis-relevant pathway effects. Indirect only Plausible low-to-moderate adjunct; evidence is not PsA-specific.
EGCG / Green tea catechins IL-17 / IL-23-related inflammation; oxidative stress; keratinocyte hyperproliferation Immune-regulatory and antioxidant effects; mainly supported in psoriasis/preclinical models. Mostly psoriasis / preclinical Interesting adjunct, but not proven for PsA joints.
Sulforaphane KEAP1-NRF2; oxidative stress; TH17-related inflammation; autoimmune signaling Strong redox / NRF2 rationale with anti-inflammatory effects in preclinical models. Preclinical / indirect Good mechanistic candidate for the NRF2-redox tier.
Quercetin NF-κB; PI3K/AKT/GLUT1; inflammatory cell signaling Multi-target anti-inflammatory effects with arthritis relevance. Weak direct PsA evidence Mechanistically attractive, clinically still speculative for PsA.
Resveratrol NF-κB; oxidative stress; inflammatory mediators; SIRT1/AMPK-linked effects May reduce inflammatory signaling and support metabolic/redox regulation. Very limited for PsA Interesting but not near the top for real-world PsA use.
Piperlongumine NLRP3 inflammasome; ROS-sensitive inflammatory signaling; FLS proliferation/migration; MMPs Research-stage anti-inflammatory candidate with RA/psoriasis-model relevance. Research-stage only Experimental; not a practical PsA supplement at present.
Shikonin JAK/STAT; TNF-driven synoviocyte signaling; macrophage polarization; psoriasis inflammation Biologically interesting for synovitis and immune-cell signaling. Research-stage only Experimental; mainly of mechanistic interest.


Scientific Papers found: Click to Expand⟱
2201- SK,    Shikonin promotes ferroptosis in HaCaT cells through Nrf2 and alleviates imiquimod-induced psoriasis in mice
- in-vitro, PSA, HaCaT - in-vivo, NA, NA
*eff↑, *IL6↓, *IL17↓, *TNF-α↓, *lipid-P↑, *NRF2↓, *HO-1↝, *NCOA4↝, *GPx4↓, *Ferroptosis↓, *Inflam↓, *ROS↓, *Iron↓,

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,   Iron↓, 1,   lipid-P↑, 1,   NRF2↓, 1,   ROS↓, 1,  

Metal & Cofactor Biology ⓘ

NCOA4↝, 1,  

Cell Death ⓘ

Ferroptosis↓, 1,  

Immune & Inflammatory Signaling ⓘ

IL17↓, 1,   IL6↓, 1,   Inflam↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  
Total Targets: 15

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:74  Cells:%  prod#:%  Target#:226  State#:%  Dir#:1
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