| 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 |
| 3363- | QC, | The Protective Effect of Quercetin on Endothelial Cells Injured by Hypoxia and Reoxygenation |
| - | in-vitro, | Nor, | HBMECs |
| 3367- | QC, | Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments |
| - | Review, | Stroke, | NA | - | Review, | AD, | NA |
| 3369- | QC, | Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects |
| - | Review, | Pca, | NA |
| 6417- | RES, | CUR, | Curcumin and Resveratrol Synergy: A Multi-Target Strategy Against Neurodegenerative Disease Pathology |
| - | Review, | AD, | NA |
| 2650- | RES, | Oxidative Stress Inducers in Cancer Therapy: Preclinical and Clinical Evidence |
| - | Review, | Var, | NA |
| 2441- | RES, | Anti-Cancer Properties of Resveratrol: A Focus on Its Impact on Mitochondrial Functions |
| - | Review, | Var, | NA |
| 2566- | RES, | A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke |
| - | Review, | Stroke, | NA |
| 3092- | RES, | Resveratrol in breast cancer treatment: from cellular effects to molecular mechanisms of action |
| - | Review, | BC, | MDA-MB-231 | - | Review, | BC, | MCF-7 |
| 3100- | RES, | Neuroprotective effects of resveratrol in Alzheimer disease pathology |
| - | Review, | AD, | NA |
| 3071- | RES, | Resveratrol and Its Anticancer Effects |
| - | Review, | Var, | NA |
| 3052- | RES, | Resveratrol-Induced Downregulation of NAF-1 Enhances the Sensitivity of Pancreatic Cancer Cells to Gemcitabine via the ROS/Nrf2 Signaling Pathways |
| - | in-vitro, | PC, | PANC1 | - | in-vitro, | PC, | MIA PaCa-2 | - | in-vitro, | PC, | Bxpc-3 |
| 3053- | RES, | Resveratrol represses estrogen-induced mammary carcinogenesis through NRF2-UGT1A8-estrogen metabolic axis activation |
| - | in-vitro, | NA, | NA |
| 3054- | RES, | Resveratrol induced reactive oxygen species and endoplasmic reticulum stress-mediated apoptosis, and cell cycle arrest in the A375SM malignant melanoma cell line |
| - | in-vitro, | Melanoma, | A375 |
| 3057- | RES, | The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 3059- | RES, | Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury |
| - | in-vivo, | Nor, | HK-2 |
| 3060- | RES, | Resveratrol targeting NRF2 disrupts the binding between KEAP1 and NRF2-DLG motif to ameliorate oxidative stress damage in mice pulmonary infection |
| - | in-vitro, | Nor, | RAW264.7 | - | in-vivo, | NA, | NA |
| 3062- | RES, | Resveratrol enhances post-injury muscle regeneration by regulating antioxidant and mitochondrial biogenesis |
| - | in-vivo, | Nor, | NA |
| 3061- | RES, | The Anticancer Effects of Resveratrol: Modulation of Transcription Factors |
| - | Review, | Var, | NA |
| 1511- | RES, | Chemo, | Combination therapy in combating cancer |
| - | Review, | NA, | NA |
| 882- | RES, | Resveratrol: A Double-Edged Sword in Health Benefits |
| - | Review, | NA, | NA |
| 3616- | RosA, | Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders |
| - | Review, | AD, | NA |
| 3615- | RosA, | Potential Therapeutic Use of the Rosemary Diterpene Carnosic Acid for Alzheimer's Disease, Parkinson's Disease, and Long-COVID through NRF2 Activation to Counteract the NLRP3 Inflammasome |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3018- | RosA, | Rosemary (Rosmarinus officinalis L.) polyphenols and inflammatory bowel diseases: Major phytochemicals, functional properties, and health effects |
| - | Review, | IBD, | NA |
| 3004- | RosA, | Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system |
| - | in-vitro, | Nor, | HSC-T6 |
| 3002- | RosA, | Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols |
| - | Review, | Var, | NA |
| 3001- | RosA, | Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review |
| - | Review, | Var, | NA |
| 3030- | RosA, | Anticancer Activity of Rosmarinus officinalis L.: Mechanisms of Action and Therapeutic Potentials |
| - | Review, | Var, | NA |
| 1748- | RosA, | The Role of Rosmarinic Acid in Cancer Prevention and Therapy: Mechanisms of Antioxidant and Anticancer Activity |
| - | Review, | Var, | NA |
| 4994- | Sal, | Rad, | Salinomycin overcomes radioresistance in nasopharyngeal carcinoma cells by inhibiting Nrf2 level and promoting ROS generation |
| 4908- | Sal, | Salinomycin triggers prostate cancer cell apoptosis by inducing oxidative and endoplasmic reticulum stress via suppressing Nrf2 signaling |
| - | in-vitro, | Pca, | PC3 | - | in-vitro, | Pca, | DU145 |
| 5139- | SAS, | Sulfasalazine induces ferroptosis in osteosarcomas by regulating Nrf2/SLC7A11/GPX4 signaling axis |
| - | in-vitro, | OS, | MG63 | - | in-vitro, | OS, | U2OS |
| 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 |
| 4726- | Se, | Oxy, | Oxygen therapy accelerates apoptosis induced by selenium compounds via regulating Nrf2/MAPK signaling pathway in hepatocellular carcinoma |
| - | in-vivo, | HCC, | NA |
| 4729- | Se, | Selenium regulates Nrf2 signaling to prevent hepatotoxicity induced by hexavalent chromium in broilers |
| 4730- | Se, | Association between plasma selenium level and NRF2 target genes expression in humans |
| - | Human, | Nor, | NA |
| 4736- | Se, | SFN, | Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells |
| - | in-vitro, | Nor, | CCD841 |
| 4737- | Se, | Rad, | Nrf2-modulation by seleno-hormetic agents and its potential for radiation protection |
| - | in-vivo, | Var, | NA |
| 4738- | Se, | doxoR, | Selenium Attenuates Doxorubicin-Induced Cardiotoxicity Through Nrf2-NLRP3 Pathway |
| - | NA, | Nor, | NA |
| 4722- | Se, | The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis |
| - | Review, | Var, | NA |
| 4734- | SeNPs, | CPT-11, | Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles |
| - | in-vitro, | CRC, | HCT8 | - | in-vivo, | NA, | NA |
| 4735- | SeNPs, | Selenium triggers Nrf2-AMPK crosstalk to alleviate cadmium-induced autophagy in rabbit cerebrum |
| - | in-vivo, | Nor, | NA |
| 4200- | SFN, | Sulforaphane activates anti-inflammatory microglia, modulating stress resilience associated with BDNF transcription |
| - | in-vitro, | NA, | NA |
| 4202- | SFN, | Regulation of BDNF transcription by Nrf2 and MeCP2 ameliorates MPTP-induced neurotoxicity |
| - | Review, | Park, | NA |
| 4201- | SFN, | Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents |
| - | in-vivo, | NA, | NA |
| 4199- | SFN, | Sulforaphane and Brain Health: From Pathways of Action to Effects on Specific Disorders |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3180- | SFN, | Exploring the therapeutic effects of sulforaphane: an in-depth review on endoplasmic reticulum stress modulation across different disease contexts |
| - | Review, | Var, | NA |
| 3193- | SFN, | Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress |
| - | Review, | Var, | NA |
| 3184- | SFN, | The Integrative Role of Sulforaphane in Preventing Inflammation, Oxidative Stress and Fatigue: A Review of a Potential Protective Phytochemical |
| - | Review, | Nor, | NA |
| 3192- | SFN, | Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention |
| - | in-vitro, | Pca, | PC3 |
| 3663- | SFN, | Efficacy of Sulforaphane in Neurodegenerative Diseases |
| - | Review, | AD, | NA | - | Review, | Park, | 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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