期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 84, 期 -, 页码 289-295出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2015.03.033
关键词
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资金
- NIH [U01 CA166800, R01 CA169046, R01 GM073929, P30 CA086862]
- Medical Research Service, Department of Veterans Affairs [1I01BX001318-01A2]
- Carver College of Medicine
- Iowa City Veteran's Administration Medical Center
- Holden Comprehensive Cancer Center
Pharmacological ascorbate has been shown to induce toxicity in a wide range of cancer cell lines. Pharmacological ascorbate in animal models has shown promise for use in cancer treatment. At pharmacological concentrations the oxidation of ascorbate produces a high flux of H2O2 via the formation of ascorbate radical (Asc(center dot-)) The rate of oxidation of ascorbate is principally a function of the level of catalytically active metals. Iron in cell culture media contributes significantly to the rate of H2O2 generation. We hypothesized that increasing intracellular iron would enhance ascorbate-induced cytotoxicity and that iron chelators could modulate the catalytic efficiency with respect to ascorbate oxidation. Treatment of cells with the iron-chelators deferoxamine (DFO) or dipyridyl (DPD) in the presence of 2 mM ascorbate decreased the flux of H2O2 generated by pharmacological ascorbate and reversed ascorbate-induced toxicity. Conversely, increasing the level of intracellular iron by preincubating cells with Fe-hydroxyquinoline (HQ) increased ascorbate toxicity and decreased clonogenic survival. These findings indicate that redox metal metals, e.g., Fe3+/Fe2+, have an important role in ascorbate-induced cytotoxicity. Approaches that increase catalytic iron could potentially enhance the cytotoxicity of pharmacological ascorbate in vivo. Published by Elsevier Inc.
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