Induction of myelogenous leukemia cells with histone deacetylase inhibitors through down-regulating the Daxx protein expression

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2009-10, Vol.29 (5), p.546-550
• Main Authors: Li, Chunrui, Zhou, Jianfeng, Wu, Xueqiong, Tian, Ye, Deng, Jingniu, Liu, Wenli
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Apoptosis - drug effects; bcl-X Protein - metabolism; Butyrates - pharmacology; Down-Regulation - drug effects; Histone Deacetylase Inhibitors - pharmacology; HL-60 Cells; Humans; Hydroxamic Acids - pharmacology; K562 Cells; Medicine; Medicine & Public Health; Nuclear Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - metabolism
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-009-0504-7

Summary The effects of two different histone deacetylase (HDAC) inhibitors, sodium butyrate (NaB) and trichostatin A (TSA),on apoptosis of human leukemic cells in vitro and the molecular mechanisms were investigated. The experiments were divided up 5 groups: control group, NaB group, TSA group, NaB+Z-VAD-FMK group and TSA+Z-VAD-FMK group. The apoptosis rate was determined by morphological analysis and flow cytomytry. The expression of Daxx, Bcl-2, and Bcl-xl proteins was detected by Western blot. NaB and TSA could induce the apoptosis of HL-60 and K562 cells, and Z-VAD-FMK caused a marked decrease in apoptosis induced by HDAC inhibitors. HDAC inhibitors could down-regulate the expression of Daxx protein, but had no significant influence on the expression of Bcl-2 and Bcl-xl proteins. The results suggested that NaB and TSA induce distinct caspase-dependent apoptosis of human leukemic cells through down-regulating the expression of Daxx protein in vitro .