Downregulation of c-Myc is critical for valproic acid-induced growth arrest and myeloid differentiation of acute myeloid leukemia

Yun Chih Cheng, Hsiupen Lin, Ming Jer Huang, Jyh-Ming Chow, Shufan Lin, Hsingjin-Eugene Liu

研究成果: 雜誌貢獻文章同行評審

47 引文 斯高帕斯(Scopus)

摘要

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. VPA not only inhibited the growth of HL-60, U937 and NB4 cells by causing cell-cycle arrest at G0/G1 phase and apoptosis, but also induced morphologic and phenotypic changes. VPA markedly increased p21WAF1, 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.
原文英語
頁(從 - 到)1403-1411
頁數9
期刊Leukemia Research
31
發行號10
DOIs
出版狀態已發佈 - 10月 2007

ASJC Scopus subject areas

  • 癌症研究
  • 血液學
  • 腫瘤科

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