Pharmacologic Doses of Ascorbate Act As a Prooxidant and Decrease Growth of Aggressive Tumor Xenografts in Mice

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2008 Aug 6

PMID 18678913

Citations 332

Authors

Qi Chen

Michael Graham Espey

Andrew Y Sun

Chaya Pooput

Kenneth L Kirk

Murali C Krishna

Deena Beneda Khosh

Jeanne Drisko

Mark Levine

Affiliations

Soon will be listed here.

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.

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