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Blood, 15 May 2005, Vol. 105, No. 10, pp. 4004-4012. Prepublished online as a Blood First Edition Paper on January 27, 2005; DOI 10.1182/blood-2003-03-0772. This Article Full Text (PDF) All Versions of this Article: 2003-03-0772v1 105/10/4004    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Karasavvas, N. Articles by Golde, D. W Search for Related Content PubMed PubMed Citation Articles by Karasavvas, N. Articles by Golde, D. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 12, 2003 Accepted January 11, 2005 Vitamin C protects HL60 and U266 cells from arsenic toxicity Nicos Karasavvas, Juan M Carcamo*, George Stratis, and David W Golde Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Clinical Laboratories, Memorial Sloan-Kettering Cancer Center, New York, NY, USA Program in Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA * Corresponding author; email: carcamoj{at}mskmail.mskcc.org. Although there is no compelling evidence that vitamin C has anti-tumor activity in humans, clinical trials are testing the hypothesis that ascorbic acid (AA) will enhance the efficacy of arsenic trioxide (As2O3) in myeloma. In vitro, AA cytoxicity depends on its interaction with free transition metal ions in culture media leading to the generation of H2O2 and other reactive oxygen species (ROS). Therefore, to circumvent the extracellular in vitro pro-oxidant effects of AA, we loaded HL60, U266 and RPMI-8226 cells with vitamin C by incubation with dehydroascorbic acid (DHA). Loading cells in this manner resulted in prominent, dose-dependent protection of As2O3 treated cells as measured by viability, colony formation, and apoptosis assays. Glutathione depletion enhanced cell sensitivity to the cytotoxic effects of As2O3 and vitamin C loading provided protection. AA was found to generate cytotoxic concentrations of H2O2 in culture medium without cells and copper/iron chelators inhibited this reaction. However, AA did not generate H2O2 in simple buffer or human plasma. Direct incubation with AA resulted in increased intracellular ROS, whereas DHA incubation decreased it. These results clarify an apparent paradox and indicate that vitamin C loading in HL60, U266 and RPMI-8226 cells ameliorates As2O3 cytotoxicity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. R. Berenson, J. Matous, R. A. Swift, R. Mapes, B. Morrison, and H. S. Yeh A Phase I/II Study of Arsenic Trioxide/Bortezomib/Ascorbic Acid Combination Therapy for the Treatment of Relapsed or Refractory Multiple Myeloma Clin. Cancer Res., March 15, 2007; 13(6): 1762 - 1768. [Abstract] [Full Text] [PDF] L. Catley and K. C. Anderson Velcade and Vitamin C: Too Much of a Good Thing? Clin. Cancer Res., January 1, 2006; 12(1): 3 - 4. [Full Text] [PDF]

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