| Potentiation of arsenic trioxide-induced apoptosis by 8-bromo-7-methoxychrysin in human leukemia cells involves depletion of intracellular reduced glutathione. | |
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MedLine Citation:
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PMID: 21785114 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The novel chrysin analog 8-bromo-7-methoxychrysin (BrMC) has been reported to induce apoptosis of various cancer cell lines. Arsenic trioxide (ATO) treatment induces clinical remission in acute promyelocytic leukemia patients. The combination of ATO with other agents has been shown to improve therapeutic effectiveness in vitro and in vivo. In this report, the mechanism of apoptosis induced by treatment with ATO alone or in combination with BrMC was studied in U937, HL-60, and Jurkat cells. Our results demonstrated that BrMC cooperated with ATO to induce apoptosis in human leukemia cells. This co-treatment caused mitochondrial transmembrane potential dissipation and stimulated the mitochondrial apoptotic pathway, as evidenced by cytochrome c release, down-regulation of X-linked inhibitor of apoptosis (XIAP) and Bcl-XL, and up-regulation of Bax. BrMC alone or in combination with ATO, decreased Akt phosphorylation as well as intracellular reduced glutathione (GSH) content. The thiol antioxidant N-acetylcysteine and exogenous GSH restored GSH content and attenuated apoptosis induced by co-treatment with ATO plus BrMC. In contrast, the non-thiol antioxidant butylated hydroxyanisole and mannitol failed to do so. These findings suggest that GSH depletion explains at least in part the potentiation of ATO-induced apoptosis by BrMC. |
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Authors:
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Guangfen Xiao; Xueyuan Tang; Chenjiao Yao; Chenghong Wang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-23 |
Journal Detail:
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Title: Acta biochimica et biophysica Sinica Volume: - ISSN: 1745-7270 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101206716 Medline TA: Acta Biochim Biophys Sin (Shanghai) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 410013, China. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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