Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice
Qi Chen, Michael Graham Espey, Andrew Y Sun, Chaya Pooput, Kenneth L Kirk, Murali C Krishna, Deena Beneda Khosh, Jeanne Drisko, Mark Levine, Qi Chen, Michael Graham Espey, Andrew Y Sun, Chaya Pooput, Kenneth L Kirk, Murali C Krishna, Deena Beneda Khosh, Jeanne Drisko, Mark Levine
Abstract
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 hydrogen-peroxide-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 therapeutic options.
Conflict of interest statement
The authors declare no conflict of interest.
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Source: PubMed