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Cited by 1,070

The DOI matches its Crossref record; 258 of the 258 references it cites were found in a registry or an index.

Ascorbic acid: Chemistry, biology and the treatment of cancer

Open access
Du, Juan, Cullen, Joseph J., Buettner, Garry R.·2012·Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
DOI 10.1016/j.bbcan.2012.06.003
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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.

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Metadata

Authors
Du, J., Cullen, J. J., & Buettner, G. R.
Venue
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Publisher
Elsevier BV
Published
2012-12
Volume
1826
Issue
2
Pages
443-457
ISSN
0304-419X (ISSN-L)
DOI
10.1016/j.bbcan.2012.06.003
OpenAlex
W2156057127
Cited by
1,070
References
258
FWCI
39.22
Type
journal article
Language
en
Open access
green

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