Journal article
Ascorbic acid: Chemistry, biology and the treatment of cancer
Biochimica et biophysica acta. Reviews on cancer, Vol.1826(2), pp.443-457
12/2012
DOI: 10.1016/j.bbcan.2012.06.003
PMCID: PMC3608474
PMID: 22728050
Abstract
Since the discovery of vitamin C, the number of its known biological functions is continually expanding. Both the names ascorbic acid and vitamin C reflect its antiscorbutic properties due to its role in the synthesis of collagen in connective tissues. Ascorbate acts as an electron-donor keeping iron in the ferrous state thereby maintaining the full activity of collagen hydroxylases; parallel reactions with a variety of dioxygenases affect the expression of a wide array of genes, for example via the HIF system, as well as via the epigenetic landscape of cells and tissues. In fact, all known physiological and biochemical functions of ascorbate are due to its action as an electron donor. The ability to donate one or two electrons makes AscH− an excellent reducing agent and antioxidant. Ascorbate readily undergoes pH-dependent autoxidation producing hydrogen peroxide (H2O2). In the presence of catalytic metals this oxidation is accelerated. In this review, we show that the chemical and biochemical nature of ascorbate contribute to its antioxidant as well as its prooxidant properties. Recent pharmacokinetic data indicate that intravenous (i.v.) administration of ascorbate bypasses the tight control of the gut producing highly elevated plasma levels; ascorbate at very high levels can act as prodrug to deliver a significant flux of H2O2 to tumors. This new knowledge has rekindled interest and spurred new research into the clinical potential of pharmacological ascorbate. Knowledge and understanding of the mechanisms of action of pharmacological ascorbate bring a rationale to its use to treat disease especially the use of i.v. delivery of pharmacological ascorbate as an adjuvant in the treatment of cancer.
Details
- Title: Subtitle
- Ascorbic acid: Chemistry, biology and the treatment of cancer
- Creators
- Juan Du - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA, USAJoseph J Cullen - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA, USAGarry R Buettner - Department of Radiation Oncology, University of Iowa College of Medicine, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Reviews on cancer, Vol.1826(2), pp.443-457
- DOI
- 10.1016/j.bbcan.2012.06.003
- PMID
- 22728050
- PMCID
- PMC3608474
- NLM abbreviation
- Biochim Biophys Acta Rev Cancer
- ISSN
- 0304-419X
- eISSN
- 1879-2561
- Publisher
- Elsevier B.V
- Grant note
- Susan L. Bader Foundation of Hope CA137230; 1R01GM073929 / NIH Medical Research Service, Department of Veterans Affairs
- Language
- English
- Date published
- 12/2012
- Academic Unit
- Surgery; Radiation Oncology
- Record Identifier
- 9984047757002771
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