| Features: antioxidant, energy production in cell mitochondria | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alpha-Lipoic-Acid: also known as lipoic acid or thioctic acid (reduced form is dihydrolipoic acid). "Universal antioxidant" because it is both water- and fat-soluble and can neutralize free radicals. -Treatment sometimes as ALA/N (alpha-lipoic acid/low-dose naltresone) -Also done in IV -Decreases ROS production, but also has pro-oxidant role. Normal adult can take 300 milligrams twice a day with food, but they should always take a B-complex vitamin with it. Because B complex vitamins, especially thiamine, and biotin, and riboflavin, are depleted during this metabolic process. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. -It seems a paradox that LA functions as both antioxidant and prooxidant. LA functions the pro-oxidant only in special cancer cells, such as A549 and PC9 cells which should show high-level NRF2 expression and high glycolytic level. Through inhibiting PDK1 to further prohibit NRF2; LA functions as anticancer prooxidant. α-lipoic acid possesses excellent silver chelating properties. ALA → ROS ↑ (cancer cells; high dose / stressed mitochondria) ALA → ROS ↓ (normal cells; low–moderate dose) same pattern seen with: Vitamin C, Menadione, Quercetin, EGCG, Resveratrol- ALA acts as pro-Oxidant only in cancer cells:#278 - Pro-Oxidant Dose margin >100uM:#304 - Bioavailability: 80-90%, but conversion to EPA/DHA is 5-10% (and takes longer time). - AI (Adequate Intake): 1.1-1.6g/day. - human studies have shown that ALA levels decline significantly with age - 1g of ALA might achieve 500uM in the blood. - ALA is poorly soluble, lecithin has been used as an amphiphilic matrix to enhance its bioavailability. - Pilot studies or observational interventions have used flaxseed supplementation (rich in ALA) in doses providing roughly 3–4 g of ALA daily. - Flaxseed oil is even more concentrated in ALA – typical 50–60% ALA by weight. - single walnut may contain 300mg of ALA - chia oil contains 55-65% ALA. - α-LA can also be obtained from the diet through the consumption of dark green leafy vegetables and meats - ALA is more stable in chia seeds, (2grams of ALA per tablespoon) - ALA degrades when exposed to heat, light, and air. (prone to oxidation) -Note half-life 1-2 hrs. BioAv 30-40% from walnuts, 60-80% from supplements. Co-ingestion with fat improves absorption. Both fat and water soluble Pathways: - induce ROS production - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Cyt‑c↑, Caspases↑, DNA damage↑, - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓ - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, VEGF↓, FAK↓, NF-κB↓, TGF-β↓, α-SMA↓, ERK↓ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, FAK↓, ERK↓, EMT↓, - inhibits glycolysis and ATP depletion : HIF-1α↓, PKM2↓, GLUT1↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, OXPHOS↓, GRP78↑, Glucose↓, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓, Integrins↓, - small indication of inhibiting Cancer Stem Cells : CSC↓, CD24↓, β-catenin↓, - Others: PI3K↓, AKT↓, JAK↓, STAT↓, β-catenin↓, AMPK, ERK↓, JNK, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective, - Selectivity: Cancer Cells vs Normal Cells Cancer-Relevant Pathways
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| SOD1 (superoxide dismutase 1) is a key antioxidant enzyme that catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide. In several cancers including breast, lung, HCC, and others, alterations in SOD1 expression have been observed, reflecting its role in managing oxidative stress. • Elevated SOD1 levels are sometimes associated with aggressive tumor behavior, therapy resistance, or decreased apoptosis due to enhanced ROS detoxification. • Conversely, the protective role of antioxidants can also mitigate oxidative mutation loads, leading to context-dependent and occasionally favorable outcomes. In non-small cell lung cancer (NSCLC), increased SOD1 levels have been reported in some cohorts, potentially as a mechanism to cope with high reactive oxygen species (ROS) levels. |
| 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 |
| 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 |
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#:29 Target#:1052 State#:% Dir#:2
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