| Features: micronutrient | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Naturally occurring element. Selenium is incorporated into selenoproteins, such as glutathione peroxidases (GPxs) and thioredoxin reductases (TrxRs), which play critical roles in protecting cells from oxidative damage. Involved in GPx, TrxR, ans Selenoprotien P which protect normal cells from oxidative stress. Important in Thyroid hormone metabolism, immune system regulation, reproductive health, and Brain and heart protection. -recommended daily allowance (RDA) for selenium is about 55 µg/day for adults. (upper tolerance 400ug/day) -One Brazil nut may contain 50-300ug/nut Sodium selenite (Na₂SeO₃) is a selenium compound with well-documented anticancer and chemopreventive properties -Oxidation state: +4 (selenite form of selenium) -Type: Inorganic selenium compound (water-soluble) -Sodium selenite generates reactive oxygen species (ROS) selectively in tumor cells. -Induces cytochrome c release, caspase-3 activation, and DNA fragmentation. -Reduces VEGF expression and endothelial cell migration. -Blocks cell division at G2/M phase -Suppresses MMP-2 and MMP-9 activity -Activates p53 -Inhibits NF-κB -PI3K/Akt/mTOR Suppression -Inactivation of Thioredoxin/Glutathione systems -NRF2 inhibition in cancer cell might be connected with O2 level Narrow therapeutic window: -Low micromolar (≤5 µM) → anticancer -High (>10 µM) → toxic to normal cells Some Selenium Supplements use Sodium Selenite as the active ingredient. - NOW Foods Selenium, Nature's Bounty Selenium, etc Other common form is Selenomethionine, as it is better absorbed (found in brazil nuts), but might be less effective? | Category | Role in cancer | | -------------------------------- | ----------------------------------------------------------------------------------------------- | | Sodium Selenium (selenite) | Direct cytotoxic redox poison | | Selenium (organic / nutritional) | **Redox buffer & immune modulator** (generally *anti-therapy* when oxidative stress is desired) | | SeNPs | Tunable redox-signaling anticancer platform | Selenium (Organic / Nutritional) — Cancer-Relevant Pathways
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| 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 |
| 3517- | Bor, | Se, | The protective effects of selenium and boron on cyclophosphamide-induced hepatic oxidative stress, inflammation, and apoptosis in rats |
| - | in-vivo, | Nor, | NA |
| 4722- | Se, | The Yin and Yang of Nrf2-Regulated Selenoproteins in Carcinogenesis |
| - | Review, | Var, | NA |
| 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 |
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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