| 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 |
| 2915- | LT, | Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells |
| - | in-vitro, | Colon, | HT29 | - | in-vitro, | CRC, | SNU-407 | - | in-vitro, | Nor, | FHC |
| 2919- | LT, | Luteolin as a potential therapeutic candidate for lung cancer: Emerging preclinical evidence |
| - | Review, | Var, | NA |
| 2916- | LT, | Antioxidative and Anticancer Potential of Luteolin: A Comprehensive Approach Against Wide Range of Human Malignancies |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 2595- | LT, | Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management? |
| - | Review, | Var, | NA |
| 4292- | LT, | Luteolin for neurodegenerative diseases: a review |
| - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | MS, | NA | - | Review, | Stroke, | NA |
| 4883- | LT, | CHr, | BRU, | VitC, | An update of Nrf2 activators and inhibitors in cancer prevention/promotion |
| - | Review, | Var, | NA |
| 8345- | Lut, | Lutein inhibits breast cancer cell growth by suppressing antioxidant and cell survival signals and induces apoptosis |
| - | in-vitro, | BC, | MCF7 | - | in-vitro, | BC, | MDA-MB-231 |
| 8343- | Lut, | Association of Lutein with Cancer: A Systematic Review of the Lutein Effects on Cellular Processes Involved in Cancer Progression |
| - | Review, | Var, | NA |
| 8344- | Lut, | NrF2/ARE and NF-κB pathway regulation may be the mechanism for lutein inhibition of human breast cancer cell |
| - | in-vitro, | BC, | NA |
| 3531- | Lyco, | Lycopene attenuates the inflammation and apoptosis in aristolochic acid nephropathy by targeting the Nrf2 antioxidant system |
| - | in-vivo, | Nor, | NA |
| 3532- | Lyco, | Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer’s disease |
| - | in-vitro, | AD, | NA |
| 3528- | Lyco, | The Importance of Antioxidant Activity for the Health-Promoting Effect of Lycopene |
| - | Review, | Nor, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 3828- | Lyco, | Lycopene alleviates oxidative stress via the PI3K/Akt/Nrf2pathway in a cell model of Alzheimer's disease |
| - | in-vitro, | AD, | M146L |
| 3268- | Lyco, | Lycopene as a Natural Antioxidant Used to Prevent Human Health Disorders |
| - | Review, | AD, | NA |
| 3264- | Lyco, | Pharmacological potentials of lycopene against aging and aging‐related disorders: A review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 3275- | Lyco, | Multifaceted Effects of Lycopene: A Boulevard to the Multitarget-Based Treatment for Cancer |
| - | Review, | Var, | NA |
| 8421- | Lyco, | Lycopene: Sojourn from kitchen to an effective therapy in Alzheimer's disease |
| - | Review, | AD, | NA |
| 8416- | Lyco, | Lycopene alleviates cognitive dysfunctions in an Alzheimer's disease rat model via suppressing the oxidative and neuroinflammatory signaling |
| - | in-vivo, | AD, | NA |
| 8414- | Lyco, | Exploring the Therapeutic Potential of Lycopene: Mechanisms, Biological Activities, and Health Benefits |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 4228- | Lyco, | A review for the pharmacological effect of lycopene in central nervous system disorders |
| - | Review, | AD, | NA | - | Review, | Park, | NA |
| 4230- | Lyco, | Supplementation of lycopene attenuates oxidative stress induced neuroinflammation and cognitive impairment via Nrf2/NF-κB transcriptional pathway |
| - | in-vivo, | AD, | NA |
| 4800- | Lyco, | Recent insights on pharmacological potential of lycopene and its nanoformulations: an emerging paradigm towards improvement of human health |
| - | Review, | Var, | NA |
| 4780- | Lyco, | Potential inhibitory effect of lycopene on prostate cancer |
| - | Review, | Pca, | NA |
| 4797- | Lyco, | A mechanistic updated overview on lycopene as potential anticancer agent |
| - | Review, | Var, | NA |
| 4795- | Lyco, | Updates on the Anticancer Profile of Lycopene and its Probable Mechanism against Breast and Gynecological Cancer |
| - | Review, | BC, | NA |
| 1709- | Lyco, | Lycopene prevents carcinogen-induced cutaneous tumor by enhancing activation of the Nrf2 pathway through p62-triggered autophagic Keap1 degradation |
| - | in-vitro, | Nor, | JB6 |
| 1708- | Lyco, | The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies |
| - | Review, | Var, | NA |
| 5252- | MAG, | Insights on the Multifunctional Activities of Magnolol |
| - | Review, | Var, | NA |
| 8514- | MAG, | Magnolol alleviates Alzheimer's disease-like pathology in transgenic C. elegans by promoting microglia phagocytosis and the degradation of beta-amyloid through activation of PPAR-γ |
| - | in-vivo, | AD, | NA |
| 8526- | Matr, | A Systematic Review of the Pharmacology, Toxicology and Pharmacokinetics of Matrine |
| - | Review, | Nor, | NA |
| 8544- | Matr, | Matrine in Liver Diseases: Mechanistic Insights and Therapeutic Potential |
| - | Review, | BC, | NA |
| 8552- | Matr, | Matrine exerts its neuroprotective effects by modulating multiple neuronal pathways |
| - | Review, | AD, | NA |
| 8549- | Matr, | Matrine disrupts Nrf2/GPX4 antioxidant system and promotes hepatocyte ferroptosis |
| - | in-vitro, | Var, | NA |
| 8816- | MCP, | Modified citrus pectin inhibits breast cancer development in mice by targeting tumor-associated macrophage survival and polarization in hypoxic microenvironment |
| - | vitro+vivo, | BC, | MDA-MB-231 | - | in-vitro, | BC, | 4T1 |
| 8756- | MeSA, | THE MAIN CYTOTOXIC EFFECTS OF METHYLSELENINIC ACID ON VARIOUS CANCER CELLS |
| - | Review, | Var, | NA |
| 8762- | MeSA, | Methylseleninic Acid Sensitizes Ovarian Cancer Cells to T-Cell Mediated Killing by Decreasing PDL1 and VEGF Levels |
| - | in-vitro, | Ovarian, | A2780S |
| 6538- | MeSal, | ASA, | Salicylate induces AMPK and inhibits c-MYC to activate a NRF2/ARE/miR-34a/b/c cascade resulting in suppression of colorectal cancer metastasis |
| - | in-vitro, | CRC, | NA |
| 1204- | MET, | Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer |
| - | in-vitro, | Lung, | A549 | - | in-vitro, | Lung, | H1299 |
| 5785- | MET, | Metformin improves healthspan and lifespan in mice |
| - | in-vivo, | Nor, | NA |
| 3457- | MF, | Cellular stress response to extremely low‐frequency electromagnetic fields (ELF‐EMF): An explanation for controversial effects of ELF‐EMF on apoptosis |
| - | Review, | Var, | NA |
| 4105- | MF, | Extremely low frequency electromagnetic fields stimulation modulates autoimmunity and immune responses: a possible immuno-modulatory therapeutic effect in neurodegenerative diseases |
| - | Review, | AD, | NA |
| 3462- | MF, | The Effect of a Static Magnetic Field on microRNA in Relation to the Regulation of the Nrf2 Signaling Pathway in a Fibroblast Cell Line That Had Been Treated with Fluoride Ions |
| - | in-vitro, | Nor, | NA |
| 9157- | MG, MIC-1, | Isothiocyanate-enriched moringa seed extract alleviates ulcerative colitis symptoms in mice |
| - | in-vivo, | Col, | NA |
| 9087- | MGF, | Mangiferin in human disease: Multifaceted mechanisms and applications (Review) |
| - | Review, | Var, | NA |
| 1780- | MLT, | Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing |
| - | Review, | Var, | NA |
| 8672- | MLT, | Glioblastoma and Melatonin’s Effects: A Narrative Review |
| - | Review, | GBM, | NA |
| 8689- | MLT, | Role of melatonin in Alzheimer's disease: From preclinical studies to novel melatonin-based therapies |
| - | Review, | AD, | NA |
| 8687- | MLT, | Melatonin induces cell cycle arrest and suppresses tumor invasion in urinary bladder urothelial carcinoma |
| - | in-vitro, | CRC, | T24/HTB-9 | - | in-vitro, | Bladder, | UMUC3 |
| 8673- | MLT, | Therapeutic Potential of Melatonin in Gastrointestinal Cancers: Molecular Mechanisms, Preclinical Evidence and Clinical Implications |
| - | Review, | GC, | NA |
| 8613- | MO, | Unraveling the Effects of Melissa officinalis L. on Cognition and Sleep Quality: A Narrative Review |
| - | Review, | AD, | 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
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