Proposed mechanism
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Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and h... - 0 views
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The data show that pharmacologic ascorbate concentrations produced Asc•− selectively in extracellular fluid compared with blood and that H2O2 formation occurred when Asc•− concentrations were >100 nM in extracellular fluid.
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These data validate the hypothesis that ascorbate is a prodrug for selective delivery of reactive species to the extravascular space
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Recently we reported that pharmacologic ascorbic acid concentrations produced H2O2 concentrations of ≥25 μM, causing cancer cell death in vitro
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We found that H2O2 concentrations generated in vivo were those that caused cancer cell death in vitro
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When ascorbate was given parenterally, Asc•−, the product of a loss of one electron from ascorbate, was detected preferentially in extracellular fluid compared with blood
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Asc•− generation in extracellular fluid depended on the ascorbate dose and the resulting concentrations
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With i.v. administration of ascorbate, Asc•− concentrations were as much as 12-fold greater in extracellular fluid compared to blood and approached 250 nM
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These data are all consistent with the hypothesis that pharmacologic ascorbate concentrations in vivo serve as a prodrug for selective delivery of H2O2 to the extracellular space
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After oral ingestion, control of intracellular and extracellular ascorbate concentrations is mediated by three mechanisms: intestinal absorption, tissue transport, and renal reabsorption
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intestinal absorption, or bioavailability, declines at doses >200 mg
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corresponding to plasma concentrations of ≈60 μM
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at approximately this concentration, the ascorbate tissue transporter SVCT2 approaches Vmax, and tissues appear to be saturated
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Temporarily bypassing tight control with parenteral administration of ascorbate allows H2O2 to form in discrete time periods only, decreasing likelihood of harm, and provides a pharmacologic basis for therapeutic use of i.v. ascorbate
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In addition to cancer treatment, another potential therapeutic use is for treatment of infections. H2O2 concentrations of 25–50 μM are bacteriostatic
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Ascorbic Acid Chemosensitizes Colorectal Cancer Cells and Synergistically Inhibits Tumo... - 0 views
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pharmacological concentrations of AA were capable of inducing anti-proliferative, cytotoxic and genotoxic effects
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pharmacological concentrations of AA can sensitize cancer cells to chemotherapy, enhancing its antineoplastic effect
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synergistic effect with conventional chemotherapeutic drugs is a fact already reported, in various types of cancer, by numerous authors, namely in pancreatic (Espey et al., 2011), prostate (Gilloteaux et al., 2014), lung (Lee et al., 2017), breast (Kurbacher et al., 1996; Wu et al., 2017) and ovarian (Ma et al., 2014) cancers.
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chemosensitizing effect of vitamin C has already been proven by several authors in various types of cancer
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intravenous pharmacological concentrations, may not only potentiate the effects of conventional chemotherapy, but also improve the quality of life of cancer patients
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Combined treatment induced a reduction of 11.5% and 43% in cell viability compared with AA or Iri therapies, respectively, emphasizing the synergistic effect
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cytotoxic effect occurred with treatment with Iri alone, but also this effect was further potentiated by the presence of AA.
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association of AA with Oxa showed very promising results, considering that a synergistic effect was demonstrated, in almost all conditions
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AA and Oxa seem to act synergistically by the activation of the intrinsic pathway of apoptosis, translated on the statistically significant increase of the ratio between BAX and BCL-2 proteins, which in turn is associated with a decrease of Δψm
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Previous results obtained by our group showed that AA mediates reactive oxygen species (ROS) formation capable of irreparably damaging DNA