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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) |
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| Type: enzymes |
| Tricarboxylic Acid (TCA) cycle, also known as the Citric Acid cycle or Krebs cycle, is a key metabolic pathway that plays a central role in cellular energy production. The TCA cycle is a series of chemical reactions that occur in the mitochondria and involve the breakdown of acetyl-CoA, a molecule produced from the breakdown of carbohydrates, fats, and proteins. The TCA cycle produces: 1. NADH and FADH2 2. ATP 3. GTP Expression of TCA cycle enzymes is often downregulated in cancer cells. Since cancer cells often exhibit rewired metabolism, including alterations in the use of the TCA cycle, researchers are exploring potential therapeutic interventions that target metabolic enzymes or pathways. TCA cycle is essential for normal cellular metabolism, its role in cancer is multifaceted. Cancer cells often reprogram their metabolism—including the TCA cycle—to support rapid growth, adapt to hypoxia, and manage oxidative stress. Mutations in key TCA cycle enzymes generate oncometabolites that further contribute to cancer progression by disrupting normal cellular regulation. Rather than saying the TCA cycle is globally over- or underexpressed in cancer, it is more accurate to say that cancer cells reprogram the cycle—with selective upregulation of parts important for biosynthesis and survival and mutations or downregulation of other parts—to best support their growth and survival in a challenging microenvironment. Oncometabolites -Some metabolites in the Krebs cycle, when accumulated to abnormal levels due to genetic mutations or enzyme deficiencies, are termed “oncometabolites” because they can promote tumorigenesis. -Mutations in succinate dehydrogenase (SDH) can lead to accumulation of succinate. -Mutations in fumarate hydratase (FH) result in an accumulation of fumarate. -Mutations in isocitrate dehydrogenase (IDH1 and IDH2) result in a neomorphic enzyme activity that converts α-ketoglutarate (α-KG) to 2-hydroxyglutarate: |
| 630- | VitC, | Metabolomic alterations in human cancer cells by vitamin C-induced oxidative stress |
| - | in-vitro, | BC, | MCF-7 | - | in-vitro, | BC, | HT-29 |
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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