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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Dai, J. Articles by Jing, Y. Search for Related Content PubMed PubMed Citation Articles by Dai, J. Articles by Jing, Y. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 93 No. 1 (January 1), 1999: pp. 268-277 Malignant Cells Can Be Sensitized to Undergo Growth Inhibition and Apoptosis by Arsenic Trioxide Through Modulation of the Glutathione Redox System Jie Dai, Rona S. Weinberg, Samuel Waxman, and Yongkui Jing From the Rochelle Belfer Chemotherapy Foundation Laboratory, the Division of Neoplastic Diseases, the Division of Hematology, the Department of Medicine, Mount Sinai Medical Center, New York, NY. Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemia (APL) with minimal toxicity and apoptosis in APL-derived NB4 cells at low (1 to 2 µmol/L) concentration. We examined the basis for NB4 cell sensitivity to As2O3 to identify experimental conditions that would render other malignant cells responsive to low concentrations of As2O3. The intracellular glutathione (GSH) content had a decisive effect on As2O3-induced apoptosis. Highly sensitive NB4 cells had the lowest GSH and the sensitivity of other cell lines was inversely proportional to their GSH content. The t(14;18) B-cell lymphoma cell line had low GSH levels and sensitivity to As2O3 at levels slightly higher than in APL cells. Experimental upmodulation of GSH content decreased the sensitivity to As2O3. Ascorbic acid and buthionine sulfoxide (BSO) decreased GSH to a greater extent, and rendered malignant cells more sensitive to As2O3. As2O3-induced apoptosis was not enhanced by ascorbic acid in normal cells, suggesting that the combination of ascorbic acid and As2O3 may be selectively toxic to some malignant cells. Ascorbic acid enhanced the antilymphoma effect of As2O3 in vivo without additional toxicity. Thus, As2O3 alone or administered with ascorbic acid may provide a novel therapy for lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. H. HAN, H. J. MOON, B. R. YOU, S. Z. KIM, S. H. KIM, and W. H. PARK The Effect of MAPK Inhibitors on Arsenic Trioxide-treated Calu-6 Lung Cells in Relation to Cell Death, ROS and GSH Levels Anticancer Res, October 1, 2009; 29(10): 3837 - 3844. [Abstract] [Full Text] [PDF] H. 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