| 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 |
| 5471- | AF, | Anti-Tumoral Treatment with Thioredoxin Reductase 1 Inhibitor Auranofin Fosters Regulatory T Cell and B16F10 Expansion in Mice |
| - | vitro+vivo, | Melanoma, | B16-F10 |
| 5470- | AF, | Exploring a Therapeutic Gold Mine: The Antifungal Potential of the Gold-Based Antirheumatic Drug Auranofin |
| - | Review, | Var, | NA |
| 5237- | AgNPs, | Nrf2 Activation Mitigates Silver Nanoparticle-Induced Ferroptosis in Hepatocytes |
| - | in-vitro, | Liver, | HepG2 |
| 5238- | AgNPs, | β-Sitosterol-assisted silver nanoparticles activates Nrf2 and triggers mitochondrial apoptosis via oxidative stress in human hepatocellular cancer cell line |
| - | in-vitro, | HCC, | HepG2 |
| 5239- | AgNPs, | NOX4- and Nrf2-mediated oxidative stress induced by silver nanoparticles in vascular endothelial cells |
| - | in-vitro, | Nor, | HUVECs |
| 4428- | AgNPs, | p38 MAPK Activation, DNA Damage, Cell Cycle Arrest and Apoptosis As Mechanisms of Toxicity of Silver Nanoparticles in Jurkat T Cells |
| - | in-vitro, | AML, | Jurkat |
| - | vitro+vivo, | Nor, | NA |
| 4561- | AgNPs, | VitC, | Cellular Effects Nanosilver on Cancer and Non-cancer Cells: Potential Environmental and Human Health Impacts |
| - | in-vitro, | CRC, | HCT116 | - | in-vitro, | Nor, | HEK293 |
| - | in-vitro, | Hepat, | HepG2 |
| 365- | AgNPs, | Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species |
| - | in-vitro, | Hepat, | HepG2 |
| 5356- | AL, | Therapeutic role of allicin in gastrointestinal cancers: mechanisms and safety aspects |
| - | Review, | GC, | NA |
| 2657- | AL, | Allicin pharmacology: Common molecular mechanisms against neuroinflammation and cardiovascular diseases |
| - | Review, | CardioV, | NA | - | Review, | AD, | NA |
| 2660- | AL, | Allicin: A review of its important pharmacological activities |
| - | Review, | AD, | NA | - | Review, | Var, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 254- | AL, | Allicin and Cancer Hallmarks |
| - | Review, | Var, | NA |
| 256- | AL, | doxoR, | Allicin Overcomes Doxorubicin Resistance of Breast Cancer Cells by Targeting the Nrf2 Pathway |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | MDA-MB-231 |
| 236- | AL, | Allicin: Chemistry and Biological Properties |
| - | Analysis, | NA, | NA |
| 3271- | ALA, | Decrypting the potential role of α-lipoic acid in Alzheimer's disease |
| - | Review, | AD, | NA |
| 3272- | ALA, | Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential |
| - | Review, | AD, | NA |
| 3456- | ALA, | Renal-Protective Roles of Lipoic Acid in Kidney Disease |
| - | Review, | NA, | NA |
| 3438- | ALA, | The Potent Antioxidant Alpha Lipoic Acid |
| - | Review, | NA, | NA | - | Review, | AD, | NA |
| 3449- | ALA, | Alpha-Lipoic Acid Downregulates IL-1β and IL-6 by DNA Hypermethylation in SK-N-BE Neuroblastoma Cells |
| - | in-vitro, | AD, | SK-N-BE |
| 3539- | ALA, | Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential |
| - | Review, | AD, | NA |
| 3541- | ALA, | Insights on alpha lipoic and dihydrolipoic acids as promising scavengers of oxidative stress and possible chelators in mercury toxicology |
| - | Review, | Var, | NA |
| 3550- | ALA, | Mitochondrial Dysfunction and Alpha-Lipoic Acid: Beneficial or Harmful in Alzheimer's Disease? |
| - | Review, | AD, | NA |
| 278- | ALA, | The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment |
| - | Review, | NA, | NA |
| 265- | ALA, | Alpha-Lipoic Acid Reduces Cell Growth, Inhibits Autophagy, and Counteracts Prostate Cancer Cell Migration and Invasion: Evidence from In Vitro Studies |
| - | in-vitro, | Pca, | LNCaP | - | in-vitro, | Pca, | DU145 |
| 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 |
| 1235- | ALA, | Cisplatin, | α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway |
| - | in-vitro, | Nor, | HEI-OC1 | - | ex-vivo, | NA, | NA |
| 1159- | And, | Andrographolide, an Anti-Inflammatory Multitarget Drug: All Roads Lead to Cellular Metabolism |
| - | Review, | NA, | NA |
| 4280- | Api, | Protective effects of apigenin in neurodegeneration: An update on the potential mechanisms |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 1547- | Api, | Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading |
| - | Review, | NA, | NA |
| 1562- | Api, | Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway |
| - | in-vitro, | Vit, | NA |
| 1561- | Api, | Apigenin Reactivates Nrf2 Anti-oxidative Stress Signaling in Mouse Skin Epidermal JB6 P + Cells Through Epigenetics Modifications |
| - | in-vivo, | Nor, | JB6 |
| 2639- | Api, | Plant flavone apigenin: An emerging anticancer agent |
| - | Review, | Var, | NA |
| 2593- | Api, | Apigenin promotes apoptosis of 4T1 cells through PI3K/AKT/Nrf2 pathway and improves tumor immune microenvironment in vivo |
| - | in-vivo, | BC, | 4T1 |
| 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 |
| 2596- | Api, | LT, | Natural Nrf2 Inhibitors: A Review of Their Potential for Cancer Treatment |
| - | Review, | Var, | NA |
| 2586- | Api, | doxoR, | Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway |
| - | in-vitro, | HCC, | Bel-7402 |
| 2318- | Api, | Apigenin as a multifaceted antifibrotic agent: Therapeutic potential across organ systems |
| - | Review, | Nor, | NA |
| 3387- | ART/DHA, | Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment |
| - | Review, | Var, | NA |
| 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 |
| 3389- | ART/DHA, | Emerging mechanisms and applications of ferroptosis in the treatment of resistant cancers |
| - | Review, | Var, | NA |
| 4278- | ART/DHA, | Artemisinin Ameliorates the Neurotoxic Effect of 3-Nitropropionic Acid: A Possible Involvement of the ERK/BDNF/Nrf2/HO-1 Signaling Pathway |
| - | in-vivo, | NA, | NA |
| 4991- | ART/DHA, | doxoR, | Dihydroartemisinin alleviates doxorubicin-induced cardiotoxicity and ferroptosis by activating Nrf2 and regulating autophagy |
| - | in-vivo, | Nor, | H9c2 |
| 4992- | ART/DHA, | Dihydroartemisinin Increases the Sensitivity of Acute Myeloid Leukemia Cells to Cytarabine via the Nrf2/HO-1 Anti-Oxidant Signaling Pathway |
| - | in-vitro, | AML, | HL-60 |
| 4993- | ART/DHA, | Dihydroartemisinin inhibits galectin-1–induced ferroptosis resistance and peritoneal metastasis of gastric cancer via the Nrf2–HO-1 pathway |
| - | vitro+vivo, | GC, | NA |
| 567- | ART/DHA, | An Untargeted Proteomics and Systems-based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells |
| - | in-vitro, | Lung, | BEAS-2B |
| 1076- | ART/DHA, | The Potential Mechanisms by which Artemisinin and Its Derivatives Induce Ferroptosis in the Treatment of Cancer |
| - | Review, | NA, | NA |
| 3174- | Ash, | Withaferin A Acts as a Novel Regulator of Liver X Receptor-α in HCC |
| - | in-vitro, | HCC, | HepG2 | - | in-vitro, | HCC, | Hep3B | - | in-vitro, | HCC, | HUH7 |
| 3173- | Ash, | Nano-targeted induction of dual ferroptotic mechanisms eradicates high-risk neuroblastoma |
| - | in-vitro, | neuroblastoma, | NA |
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#:%
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