Induction of myelogenous leukemia cells with histone deacetylase inhibitors through down-regulating the Daxx protein expression.
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.
Li
Chunrui
C
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. cunrui5650@126.com
Zhou
Jianfeng
J
Wu
Xueqiong
X
Tian
Ye
Y
Deng
Jingniu
J
Liu
Wenli
W
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology; D056970:Co-Repressor Proteins; D015536:Down-Regulation / Q000187:drug effects*; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020014:K562 Cells; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C494811:BCL2L1 protein, human; D002087:Butyrates; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C012589:trichostatin A