Pharmacologic doses of ascorbate act as a prooxidantvand decrease growth of aggressive tumor xenograftsv in miceQi Chen*†, Michael Graham Espey*†, Andrew Y. Sun*, Chaya Pooput, Kenneth L. Kirk, Murali C.Krishna, Deena Beneda Khosh, Jeanne Drisko_, and Mark Levine*
Molecular and Clinical Nutrition Section and Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, and Radiation Biology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; and _Program in Integrative Medicine, University of Kansas Medical Center, Kansas City, KS 66160
Ascorbic acid is an essential nutrient commonly regarded as an antioxidant. In this study, we showed that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogenperoxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells. To test this action in vivo, normal oral tight control was bypassed by parenteral ascorbate administration. Real-time microdialysis sampling in mice bearing glioblastoma xenografts showed that a single pharmacologic dose of ascorbate produced sustained ascorbate radical and hydrogen peroxide formation selectively within interstitial fluids of tumors but not in blood. Moreover, a regimen of daily pharmacologic ascorbate treatment significantly decreased growth rates of ovarian (P < 0.005), pancreatic (P < 0.05), and glioblastoma (P <0.001) tumors established in mice. Similar pharmacologic concentrations were readily achieved in humans given ascorbate intravenously.
These data suggest that ascorbate as a prodrug may have benefits in cancers with poor prognosis and limited therapeuticoptions.
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Vitamin C Studie Pharmacologic doses of ascorbate act as a prooxidant Studie Chen Proc Natl Acad Sci 2008