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| Menadione (2-methyl-1,4-naphthoquinone, also termed vitamin K3) Menadione-induced ROS generation is concentration-dependent and high concentrations trigger cell death. Clinical trials conducted on patients with prostate cancer showed that ascorbic acid-menadione produced an immediate drop in tumor cell numbers through a mechanism named autoschizis. Menadione (Vitamin K3) is a synthetic naphthoquinone compound. It is not used as a nutritional vitamin supplement in humans due to toxicity risk (particularly hemolysis and hepatotoxicity). Historically used in animal feed. Mechanistically, menadione functions primarily as a redox-active quinone, capable of: -Undergoing redox cycling -Generating reactive oxygen species (ROS) -Inducing oxidative stress -Interacting with glutathione (GSH) systems -Modulating mitochondrial functionIt has been investigated in oncology research largely due to its pro-oxidant cytotoxic properties, not classical vitamin K–dependent clotting roles.
Time-Scale Flag (TSF): P / R / G
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| High-dose vitamin C: Some studies have suggested that high-dose vitamin C may be effective in treating certain types of cancer, such as ovarian cancer and pancreatic cancer. Symptoms of vitamin C deficiency include fatigue, weakness, poor wound healing, ecchymoses, xerosis, lower extremity edema, and musculoskeletal pain—most of them are often observed in end-stage cancer patients. -Vitamin C is an essential nutrient involved in the repair of tissue, the formation of collagen, and the enzymatic production of certain neurotransmitters. It is required for the functioning of several enzymes and is important for immune system function. -Ascorbic Acid, Different levels in different Organs Homeostasis ranging from about 0.2 mM in the muscle and heart, and up to 10 mM in the brain and adrenal gland. -(Note the Oncomagnetic success in the brain also was then under conditions of high Vitamin C) -Ascorbic acid is an electron donor Ascorbic Acid, can be a Pro-oxidant "The pro-oxidative activity of ascorbic acid (Figure 2) is associated with the interaction with transition metal ions (especially iron and copper). Under conditions of high, millimolar ascorbate concentration, vitamin C catalyzes the reduction of free transition metal ions, which causes the formation of oxygen radicals." Ascorbic Acid, formation of H2O2 (Hydrogen Peroxide) Many studies indicate the toxicity of ascorbate to cancer cells. Much evidence indicates that the underlying phenomenon is the pro-oxidative activity of ascorbate, which induces the formation of H2O2 and oxidative stress. "ascorbate at concentrations achieved only by i.v. administration may be a pro-drug for formation of H(2)O(2)" -High dose VitC therapy may not be for those with kidney problems -Oral supplement up to 10g/day? -Direct regulator of TET↑ -caution for (G6PD-) deficient patients receiving vitamin C infusions -Note plasma half-life 30mins to 1hr, 1.5-2hr elimination half-life. oral BioAv water soluble, but has limitiations as 100mg yeilds 60uM/L in plasma, but 1000mg only yeilds 85uM/L. mM concentration are required for effectiveness on cancer cells. Hence why IV administration is common. Boosting HIF increases the intracellular uptake of oxidized VitC Pathways: - high dose induces ROS production in cancer cells. Otherwise well known antioxidant in normal cells. - ROS↑ related: MMP↓(ΔΨm), ER Stress↑, Caspases↑, DNA damage↑, cl-PARP↑, - Lowers AntiOxidant defense in Cancer Cells: NRF2↓, TrxR↓**, SOD↓, GSH↓ Catalase↓ HO1↓ GPx↓ - Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑, - lowers Inflammation : NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : NLRP3↓, IL-1β↓, TNF-α↓, IL-6↓, IL-8↓ - inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, TIMP2, IGF-1↓, VEGF↓, NF-κB↓, - reactivate genes thereby inhibiting cancer cell growth : P53↑, TET↑ - cause Cell cycle arrest : TumCCA↑, cyclin D1↓, CDK2↓, - inhibits Migration/Invasion : TumCMig↓, TumCI↓, TNF-α↓, ERK↓, EMT↓, TET1↓, - inhibits glycolysis /Warburg Effect and ATP depletion : HIF-1α↓, PKM2↓, cMyc↓, GLUT1↓, LDH↓, LDHA↓, HK2↓, PFKs↓, PDKs↓, ECAR↓, GRP78↑, Glucose↓, GlucoseCon↓ - inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, - Others: PI3K↓, AKT↓, STAT↓, AMPK, ERK↓, JNK, - Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, RadioProtective, Others(review target notes), Neuroprotective, Cognitive, Hepatoprotective, - Selectivity: Cancer Cells vs Normal Cells Selenium supplementation may protect cells against iron-dependent cell death by supporting increased expression of selenoproteins, including GPX4, which defend against oxidative stress. Meaning it may decrease effectiveness of high dose VitC.(#4468) |
| 4713- | Se, | VitC, | VitK3, | Selenium supplementation protects cancer cells from the oxidative stress and cytotoxicity induced by the combination of ascorbate and menadione sodium bisulfite |
| - | in-vitro, | GBM, | NA |
| 600- | VitC, | VitK3, | Serum markers variation consistent with autoschizis induced by ascorbic acid-menadione in patients with prostate cancer |
| - | in-vitro, | NA, | NA |
| 609- | VitC, | ALA, | VitK3, | Se, | Vitamin C and Cancer: Is There A Use For Oral Vitamin C? |
| 612- | VitC, | VitK3, | Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. I. Synergism of combined vitamin C and K3 action |
| 635- | VitC, | VitK3, | The combination of ascorbate and menadione causes cancer cell death by oxidative stress and replicative stress |
| - | in-vitro, | NA, | NA |
| 1819- | VitC, | VitK3, | The association of vitamins C and K3 kills cancer cells mainly by autoschizis, a novel form of cell death. Basis for their potential use as coadjuvants in anticancer therapy |
| - | Review, | Var, | NA |
| 1836- | VitC, | VitK3, | Chemo, | Vitamins C and K3: A Powerful Redox System for Sensitizing Leukemia Lymphocytes to Everolimus and Barasertib |
| - | in-vitro, | AML, | NA |
| 2278- | VitK2, | VitK3, | VitC, | Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect |
| - | Review, | Var, | NA |
| 1828- | VitK3, | VitC, | Pankiller effect of prolonged exposure to menadione on glioma cells: potentiation by vitamin C |
| - | in-vivo, | GBM, | NA |
| 1832- | VitK3, | VitC, | Vitamin K3 and vitamin C alone or in combination induced apoptosis in leukemia cells by a similar oxidative stress signalling mechanism |
| - | in-vitro, | AML, | K562 |
| 1835- | VitK3, | VitC, | Potential therapeutic application of the association of vitamins C and K3 in cancer treatment |
| - | Review, | Var, | NA |
| 1837- | VitK3, | VitC, | Alpha-Tocopheryl Succinate Inhibits Autophagic Survival of Prostate Cancer Cells Induced by Vitamin K3 and Ascorbate to Trigger Cell Death |
| - | in-vivo, | Pca, | 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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