期刊
LEUKEMIA RESEARCH
卷 31, 期 10, 页码 1403-1411出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2007.03.012
关键词
valproic acid; acute myeloid leukemia; c-Myc
Valproic acid (VPA), an agent used for neurological disorders, has been shown to be a novel class of histone deacetylase inhibitor (HDACI), able to induce apoptosis and myeloid differentiation of acute myeloid leukemia (AML). In this study, we examined the underlying mechanisms in VPA-mediated activities in AML cells. VIA not only inhibited the growth of HL-60, U937 and NB4 cells by causing cell-cycle arrest at G(0)/G(1) phase and apoptosis, but also induced morphologic and phenotypic changes. VIA markedly increased p21 WAF1, and downregulated c-Myc expression at transcriptional levels. Ectopic expression of wildtype c-Myc and T58A mutant significantly inhibited VPA-mediated growth inhibition. As with results from cell line studies, VPA also downregulated c-Myc levels, and induced apoptosis and myeloid differentiation of primary AML cells, leading to decreased colony-forming ability. Given the role of c-Myc in leukemogenesis, our study suggests that VPA might be a potential therapeutic agent for AML. (c) 2007 Elsevier Ltd. All rights reserved.
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