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Nathan Goodyear

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive ... - 0 views

www.pnas.org/...11105

cancer vitamin C

shared by Nathan Goodyear on 06 Oct 18 - No Cached
  • Nathan Goodyear on 06 Oct 18
     
    vitamin C inhibits tumor growth in ascorbate treated mice via prooxidant effect.
Nathan Goodyear

Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a p... - 0 views

www.pnas.org/...13604

vitamin C cancer

shared by Nathan Goodyear on 06 Oct 18 - No Cached
  • Ascorbate is transported into cells as such by sodium-dependent transporters, whereas dehydroascorbic acid is transported into cells by glucose transporters and then immediately reduced internally to ascorbate
  • Nathan Goodyear on 06 Oct 18
     
    vitamin C inhibits tumor growth via prooxidant effect of vitamin C.
Nathan Goodyear

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and h... - 0 views

www.pnas.org/...8749

cancer vitamin C

shared by Nathan Goodyear on 06 Oct 18 - No Cached
  • Nathan Goodyear on 06 Oct 18
     
    In vivo study of vitamin C IV found to produce H2O2 which is key to the prooxidant effect of vitamin C against cancer.
Nathan Goodyear

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive ... - 0 views

www.pnas.org/...11105.full

IV vitamin C vitamin C ovarian cancer pancreatic cancer glioblastoma cancer

shared by Nathan Goodyear on 26 May 13 - Cached
  • Nathan Goodyear on 26 May 13
     
    high dose IV vitamin C shown to be treatment option in Cancer.  Granted in a mouse study, but high dose IV vitamin C shown to decrease growth rates of ovarian, pancreatic, and glioblastoma cancers.
Nathan Goodyear

Acute prooxidant effects of vitamin C in... [Free Radic Biol Med. 2005] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...15917185

IV vitamin C antioxidant pro-oxidant EDTA EDTA chelation vitamin C vitamin

shared by Nathan Goodyear on 05 Jun 13 - No Cached
  • Nathan Goodyear on 05 Jun 13
     
    This study found a pro oxidant effect of the addition of 5 grams of IV vitamin C with EDTA chelation.  As dosing of IV vitamin C goes, 5 grams is quite small.  Vitamin C has been shown to have varying effects (pro oxidant versus antioxidant) dictated by the dosage.  One wonders if higher dosing IV vitamin C provides antioxidant effects?
Nathan Goodyear

Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive ... - 0 views

www.pnas.org/...0804226105.abstract

IV vitamin C IV vitamin C cancer

shared by Nathan Goodyear on 25 Sep 13 - Cached
  • Nathan Goodyear on 25 Sep 13
     
    Nice study that reveals the pharmacologic mechanism of vitamin C as a pro-oxidant in cancer cells.  Obviously, this effect is opposite that found blood.   In this study they looked at high dose IV vitamin C in the treatment of ovarian, pancreatic, and glioblastoma cancer.  Treatment was beneficial and well tolerated.
Nathan Goodyear

From the Cover: Pharmacologic doses of ascorbate act as a prooxidant and decrease growt... - 0 views

www.ncbi.nlm.nih.gov/...PMC2516281

cancer IV intravenous vitamin C IV vitamin C

shared by Nathan Goodyear on 18 Sep 13 - No Cached
  • An extensive panel of 43 tumor and 5 normal cell lines were exposed to ascorbate in vitro for ≤2 h to mimic clinical pharmacokinetics
  • effective concentration that decreased survival 50% (EC50) was determined. EC50 was <10 mM for 75% of tumor cells tested, whereas cytotoxicity was not evident in normal cells with >20 mM ascorbate
  • The addition of catalase to the medium ameliorated death of ovarian carcinoma (Ovcar5), pancreatic carcinoma (Pan02), and glioblastoma (9L) cells exposed to 10 mM ascorbate (1 h), indicating cytotoxicity was mediated by H2O2
  • ...8 more annotations...
  • A treatment dose of 4 g ascorbate/kg body weight either once or twice daily did not produce any discernible adverse effects
  • Xenograft experiments showed that parenteral ascorbate as the only treatment significantly decreased both tumor growth and weight by 41–53%
  • Peak plasma concentrations of ascorbate approached 30 mM
  • Pharmacologic concentrations of ascorbate decreased tumor volumes 41–53% in diverse cancer types known for both their aggressive growth and limited treatment options.
  • Our findings showed that pharmacologic ascorbic acid concentrations were cytotoxic to many types of cancer cells in vitro (Fig. 1A) and significantly impeded tumor progression in vivo without toxicity to normal tissues
  • The amelioration of ascorbate cytotoxicity in vitro by the addition of catalase was consistent among sensitive cancer cells (Fig. 1B) and points unambiguously to H2O2 generation in the extracellular medium
  • the current in vivo data support that pharmacologic ascorbate concentrations, which can readily be achieved in humans (Fig. 3E), diminished growth of several aggressive cancer types in mice (Fig. 2) without causing apparent adverse effects.
  • These intratumoral H2O2 concentrations of >125 μM persisted for >3 h after ascorbate administration
  • Nathan Goodyear on 18 Sep 13
     
    Tumor xenograft model in mice finds reduction in growth rates of ovarian cancer, pancreatic cancer, and glioblastoma with daily IV vitamin C.
Nathan Goodyear

Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer c... - 0 views

www.nature.com/...s41598-018-29386-7

hermetic dose response prooxidative low dose vitamin C vitamin sodium dependent vitamin C transporter High dose IV vitamin C SVCT C high dose vitamin C

shared by Nathan Goodyear on 11 Aug 22 - No Cached
  • Nathan Goodyear on 11 Aug 22
     
    Low dose vitamin C, via SVCT, increases tumor proliferation; whereas high dose decreases tumor proliferation.
Nathan Goodyear

Prooxidative inhibition against NF-κB-mediated inflammation by pharmacologica... - 0 views

www.sciencedirect.com/...S0891584922000181

vitamin C nuclear factor kappa B NF-KappaB v nuclear factor κB inflammation ascorbic acid NF-κB

shared by Nathan Goodyear on 16 Jul 22 - No Cached
  • Nathan Goodyear on 16 Jul 22
     
    The title tells it all.
Nathan Goodyear

Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and h... - 0 views

www.ncbi.nlm.nih.gov/...PMC1885574

vitamin C ascorbic acid Cancer

shared by Nathan Goodyear on 05 Mar 18 - No Cached
  • Proposed mechanism
  • 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.
  • These data validate the hypothesis that ascorbate is a prodrug for selective delivery of reactive species to the extravascular space
  • ...22 more annotations...
  • pharmacologic ascorbate as a prooxidant drug for therapeutic use.
  • Recently we reported that pharmacologic ascorbic acid concentrations produced H2O2 concentrations of ≥25 μM, causing cancer cell death in vitro
  • We found that H2O2 concentrations generated in vivo were those that caused cancer cell death in vitro
  • 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
  • Asc•− generation in extracellular fluid depended on the ascorbate dose and the resulting concentrations
  • 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
  • In blood, such Asc•− concentrations were never produced and were always <50 nM
  • 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
  • After oral ingestion, control of intracellular and extracellular ascorbate concentrations is mediated by three mechanisms: intestinal absorption, tissue transport, and renal reabsorption
  • intestinal absorption, or bioavailability, declines at doses >200 mg
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      significant limitation of gut absorption of vitamin C--at 200 mg po.
  • corresponding to plasma concentrations of ≈60 μM
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      equates to 0.06 mM.  Max blood levels found with po AA dosing has been 0.22 mM
  • at approximately this concentration, the ascorbate tissue transporter SVCT2 approaches Vmax, and tissues appear to be saturated
    • Nathan Goodyear
      Nathan Goodyear on 05 Mar 18
       
      SVCT2 Rc in gut reach max binding.
  • also at ≈60 μM, renal reabsorption approaches saturation, and excess ascorbate is excreted in urine
  • Parenteral administration bypasses tight control
  • When tight control is bypassed, H2O2 forms in the extracellular space
  • in vivo validation of ascorbate as a prodrug for selective H2O2 formation
  • 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
  • H2O2 formation results in selective cytotoxicity
  • Tumor cells are killed with exposure to H2O2 for ≤30 min
  • In vitro, killing is mediated by H2O2 rather than Asc•−
  • In addition to cancer treatment, another potential therapeutic use is for treatment of infections. H2O2 concentrations of 25–50 μM are bacteriostatic
  • virally infected cells may also be candidates
  • Nathan Goodyear on 05 Mar 18
     
    follow up invivo study to previous study from 2005.  Here, the authors prove their hypothesis that ascorbate is a prodrug for delivery of H2O2.
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