| 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 |
| Cyclooxygenase (COX)-2 overexpression has been noted in various cancers.
PI3Ks/AKT pathways are over-activated in several types of cancers. EGFR altered activity has been noted in various pathological conditions. However, its regulation is an important step in the inhibition of cancer. In this regard, EGCG shows a pivotal role in the inhibition of EGFR activity. Activating protein-1 transcription factor has been associated with pathogenesis including cancer. Activation of the sonic hedgehog (Shh) pathway is required for the growth of numerous tissues and organs and recent evidence indicates that this pathway is often recruited to stimulate growth of cancer stem cells (CSCs) and to orchestrate the reprogramming of cancer cells via epithelial mesenchymal transition (EMT). Increased expression of Nanog has been associated with the aggressive nature of certain cancers, highlighting its role in promoting cancer stem cell characteristics. The aberrant hedgehog (Hh)/GLI signaling pathway causes the formation and progression of a variety of tumors. The process of cell apoptosis is often accompanied by the destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis. Human malignancies frequently exhibit mutations in the TGF-β pathway, and overactivation of this system is linked to tumor growth by promoting angiogenesis and inhibiting the innate and adaptive antitumor immune responses50. Several studies have demonstrated that high cyclin D1 expression was observed in cancers including breast, lung, prostate, lymph node and colorectal cancers [23–25]. The oncogene c-myc, which is frequently over-expressed in cancer cells, is involved in the transactivation of most of the glycolytic enzymes including lactate dehydrogenase A (LDHA) and the glucose transporter GLUT1 [51,52]. Thus, c-myc activation is a likely candidate to promote the enhanced glucose uptake and lactate release in the proliferating cancer cell. Vimentin is overexpressed in various epithelial cancers, including prostate cancer, gastrointestinal tumors, tumors of the central nervous system, breast cancer, malignant melanoma, and lung cancer. Vimentin’s overexpression in cancer correlates well with accelerated tumor growth, invasion, and poor prognosis; however, the role of vimentin in cancer progression remains obscure. Heat shock proteins (HSPs) are normally induced under environmental stress to serve as chaperones for maintenance of correct protein folding but they are often overexpressed in many cancers, including breast cancer. Since NQO1 is highly expressed in many solid tumors, including via upregulation of Nrf2, the design of compounds activated by NQO1 and NQO1-targeted drug delivery have been active areas of research. Since increased Nrf2 gene expression is one of the main mechanisms of cancer cells in resisting chemotherapeutic drugs and survival in oxidative conditions; finding compounds with the ability to suppress Nrf2 gene expression with minimum side effects can be considered an important strategy for increasing the sensitivity of cancer cells to chemotherapy. Overexpression of c-met stimulates proliferation, migration and invasion in various types of cancer including prostate cancer. Overexpression of TGFα and EGFR by many carcinomas correlates with the development of cancer metastasis, resistance to chemotherapy and poor prognosis. More than 50% of human cancers have a mutated nonfunctional p53. |
| 5470- | AF, | Exploring a Therapeutic Gold Mine: The Antifungal Potential of the Gold-Based Antirheumatic Drug Auranofin |
| - | Review, | Var, | NA |
| 2660- | AL, | Allicin: A review of its important pharmacological activities |
| - | Review, | AD, | NA | - | Review, | Var, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | 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 |
| 3387- | ART/DHA, | Ferroptosis: A New Research Direction of Artemisinin and Its Derivatives in Anti-Cancer Treatment |
| - | Review, | Var, | NA |
| 3389- | ART/DHA, | Emerging mechanisms and applications of ferroptosis in the treatment of resistant cancers |
| - | Review, | Var, | NA |
| 3156- | Ash, | Withaferin A: From ayurvedic folk medicine to preclinical anti-cancer drug |
| - | Review, | Var, | NA |
| 3160- | Ash, | Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal |
| - | Review, | Var, | NA |
| 3166- | Ash, | Exploring the Multifaceted Therapeutic Potential of Withaferin A and Its Derivatives |
| - | Review, | Var, | NA |
| 4815- | ASTX, | The Promising Effects of Astaxanthin on Lung Diseases |
| - | Review, | Var, | NA |
| 4804- | ASTX, | Astaxanthin in cancer therapy and prevention (Review) |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 2626- | Ba, | Molecular targets and therapeutic potential of baicalein: a review |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Stroke, | NA |
| 2292- | Ba, | BA, | Baicalin and baicalein in modulating tumor microenvironment for cancer treatment: A comprehensive review with future perspectives |
| - | Review, | Var, | NA |
| 5633- | BCA, | Mechanisms Behind the Pharmacological Application of Biochanin-A: A review |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 2759- | BetA, | Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical Studies |
| - | Review, | Var, | NA |
| 5686- | BJ, | BRU, | A review of Brucea javanica: metabolites, pharmacology and clinical application |
| - | Review, | Var, | NA |
| 2775- | Bos, | The journey of boswellic acids from synthesis to pharmacological activities |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | PSA, | NA |
| 2768- | Bos, | Boswellic acids as promising agents for the management of brain diseases |
| - | Review, | Var, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA |
| 5859- | CAP, | Are We Ready to Recommend Capsaicin for Disorders Other Than Neuropathic Pain? |
| - | Review, | Var, | NA |
| 6002- | CGA, | Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials |
| - | Review, | Var, | NA | - | Review, | Diabetic, | NA | - | Review, | AD, | NA | - | Review, | Park, | NA | - | Review, | Stroke, | NA |
| 6001- | Chit, | Recent advances in engineering chitosan-based nanoplatforms in biotherapeutic multi-delivery for multi-targeted disease treatments: Promises and outlooks |
| - | Review, | Var, | HepG2 | - | Review, | AD, | NA |
| 1485- | CUR, | Chemo, | Rad, | Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs |
| - | Review, | Var, | NA |
| 4881- | CUR, | SFN, | RES, | EGCG, | Lyco | An update of Nrf2 activators and inhibitors in cancer prevention/promotion |
| - | Review, | Var, | NA |
| 2819- | CUR, | Chemo, | Curcumin as a hepatoprotective agent against chemotherapy-induced liver injury |
| - | Review, | Var, | NA |
| 2821- | CUR, | Antioxidant curcumin induces oxidative stress to kill tumor cells (Review) |
| - | Review, | Var, | NA |
| 2845- | FIS, | Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy |
| - | Review, | Var, | NA |
| 2825- | FIS, | Exploring the molecular targets of dietary flavonoid fisetin in cancer |
| - | Review, | Var, | NA |
| 2827- | FIS, | The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment |
| - | Review, | Var, | NA |
| 2829- | FIS, | Fisetin: An anticancer perspective |
| - | Review, | Var, | NA |
| 2830- | FIS, | Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent |
| - | Review, | Var, | NA |
| 2843- | FIS, | Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential |
| - | Review, | Var, | NA |
| 4029- | FulvicA, | Chemo, | Shilajit mitigates chemotherapeutic drug-induced testicular toxicity: Study on testicular germ cell dynamics, steroidogenesis modulation, and Nrf-2/Keap-1 signaling |
| - | in-vivo, | Var, | NA |
| 2516- | H2, | Hydrogen Gas in Cancer Treatment |
| - | Review, | Var, | NA |
| 2508- | H2, | Molecular hydrogen is a promising therapeutic agent for pulmonary disease |
| - | Review, | Var, | NA | - | Review, | Sepsis, | NA |
| 2868- | HNK, | Honokiol: A review of its pharmacological potential and therapeutic insights |
| - | Review, | Var, | NA | - | Review, | Sepsis, | NA |
| 2864- | HNK, | Honokiol: A Review of Its Anticancer Potential and Mechanisms |
| - | Review, | Var, | NA |
| 2894- | HNK, | Pharmacological features, health benefits and clinical implications of honokiol |
| - | Review, | Var, | NA | - | Review, | AD, | NA |
| 2914- | LT, | Therapeutic Potential of Luteolin on Cancer |
| - | 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 |
| 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 |
| 1708- | Lyco, | The Anti-Cancer Activity of Lycopene: A Systematic Review of Human and Animal Studies |
| - | Review, | Var, | NA |
| 4797- | Lyco, | A mechanistic updated overview on lycopene as potential anticancer agent |
| - | Review, | Var, | NA |
| 5252- | MAG, | Insights on the Multifunctional Activities of Magnolol |
| - | Review, | Var, | NA |
| 1780- | MEL, | Utilizing Melatonin to Alleviate Side Effects of Chemotherapy: A Potentially Good Partner for Treating Cancer with Ageing |
| - | Review, | Var, | 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 |
| 4643- | OLE, | HT, | Use of Oleuropein and Hydroxytyrosol for Cancer Prevention and Treatment: Considerations about How Bioavailability and Metabolism Impact Their Adoption in Clinical Routine |
| - | Review, | Var, | NA |
| 3251- | PBG, | The Antioxidant and Anti-Inflammatory Effects of Flavonoids from Propolis via Nrf2 and NF-κB Pathways |
| - | Review, | AD, | NA | - | Review, | Diabetic, | NA | - | Review, | Var, | NA | - | in-vitro, | Nor, | H9c2 |
| 3257- | PBG, | The Potential Use of Propolis as a Primary or an Adjunctive Therapy in Respiratory Tract-Related Diseases and Disorders: A Systematic Scoping Review |
| - | Review, | Var, | NA |
| 2946- | PL, | Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent |
| - | Review, | Var, | 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:26 Cells:% prod#:% Target#:226 State#:% Dir#:2
wNotes=0 sortOrder:rid,rpid