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KMID : 1101320060380020082
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Korean Journal of Clinical Laboratory Science
2006 Volume.38 No. 2 p.82 ~ p.86
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The Effects of Arsenic Trioxide on Cell Cycle and Apoptosis in Chronic Myelogenous Leukemia Cell Line
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Shim Moon-Jung
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Abstract
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Leukemia arises in hematopoietic progenitor cells and is characterized by impaired or blocked differentiation, uncontrolled proliferation and resistance to apoptosis. Molecular mechanisms underlying cellular functions by As2O3, however, have been poorly investigated. The consensus of several reports is that As2O3 induces apoptosis in leukemia cells by activating genes for apoptosis. The present study aimed to investigate the effects of As2O3 on the cell cycle and its morphological change and a relationship between the caspase-3 and As2O3-induced apoptosis. Caspase-3 is involved in As2O3-induced apoptosis in K562 cells. In this study, to address whether As2O3-induced apoptosis is mediated by caspase-3 activity, the same samples were probed with a specific antibody. The pretreatment of 25 μM Z-VAD-fmk, a specific inhibitor of caspase, decreased As2O3-induced cytotoxicity. And As2O3 significantly increased the percentages of the cells accumulated in the G2/M phase of the cell cycle in a time- and dose-dependent manner. Chromatin condensational changes were observed with Hoechst 33258 staining after treatment of As2O3. It was shown that As2O3-induced apoptosis is controlled through caspase-3 activation. These results may provide a useful rationale for CML treatment.
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KEYWORD
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CML, Apoptosis, Cell cycle, K562 cell, As2O3, Caspase
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