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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1198-1203. Prepublished online as a Blood First Edition Paper on July 1, 2004; DOI 10.1182/blood-2003-12-4299. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-12-4299v1 105/3/1198    most recent 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 Zhou, L. Articles by Waxman, S. Search for Related Content PubMed PubMed Citation Articles by Zhou, L. Articles by Waxman, S. Related Collections Neoplasia Apoptosis Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Glutathione-S-transferase inhibits As2O3-induced apoptosis in lymphoma cells: involvement of hydrogen peroxide catabolism Li Zhou, Yongkui Jing, Miroslav Styblo, Zhu Chen, and Samuel Waxman From the Department of Medicine, Division of Hematology/Oncology, Mount Sinai School of Medicine, New York, NY; the Department of Pediatrics and Nutrition, University of North Carolina, Chapel Hill; and the Shanghai Institute of Hematology, Rui-Jin Hospital, Shanghai Second Medical University, China. Arsenic trioxide (As2O3) is an effective agent for the treatment of relapsed and refractory acute promyelocytic leukemia by induction of partial differentiation and apoptosis. As2O3, at therapeutic concentrations (1-2 µM), induced apoptosis in Raji lymphoma cells but not in Jurkat lymphoma cells, which inversely correlated with the levels of glutathione-S-transferase (GSTP1), but not GST1 and GSTM1, expression and activity. GSTP1 mRNA, protein level, and activity were high in Jurkat cells but undetectable in Raji cells. Stable transfection of GSTP1 into Raji cells decreased the amount of As2O3-induced apoptosis. Apoptosis induced by therapeutic concentrations of As2O3 in Raji cells is related to increasing H2O2 intracellular accumulation but not to JNK activation. Forced expression of GSTP1 by transfection of Raji cells significantly decreased the basal amount of H2O2 and its levels after therapeutic concentration of As2O3 treatment. Added exogenous H2O2 was removed more rapidly, which correlated with a greater decrease in reduced glutathione level in Raji clones expressing GSTP1 than in those clones without GSTP1 expression. Overexpression of GSTP1 in transfected Raji clones was also found to decrease the retention of As2O3. These data suggest that GSTP1 blocks As2O3-induced apoptosis in lymphoma cells by decreasing intracellular amounts of H2O2 by catabolism and H2O2 production by decreasing the intracellular retention of As2O3. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Wang, C. Li, D. Song, G. Zhao, L. Zhao, and Y. Jing Ethacrynic Acid Butyl-Ester Induces Apoptosis in Leukemia Cells through a Hydrogen Peroxide Mediated Pathway Independent of Glutathione S-Transferase P1-1 Inhibition Cancer Res., August 15, 2007; 67(16): 7856 - 7864. [Abstract] [Full Text] [PDF] D. Chen, R. Chan, S. Waxman, and Y. Jing Buthionine Sulfoximine Enhancement of Arsenic Trioxide-Induced Apoptosis in Leukemia and Lymphoma Cells Is Mediated via Activation of c-Jun NH2-Terminal Kinase and Up-regulation of Death Receptors Cancer Res., December 1, 2006; 66(23): 11416 - 11423. [Abstract] [Full Text] [PDF]

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