Microarray study of mechanism of trichostatin a inducing apoptosis of Molt-4 cells.
Histone deacetylase was overexpressed in a variety of cancers and was closely correlated with oncogenic factors. The histone deacetylase inhibitor, trichostatin A (TSA) was shown to induce apoptosis in many cancer cells. However, the mechanism of TSA on induction of cancer cells apoptosis is poorly understood. This study was designed to characterize the global gene expression profiles before and after treatment of human leukemia cell line Molt-4 with TSA. Flow cytometry, MTT and DNA ladder were used to observe the effect of TSA on the apoptosis of MOLT-4 cells and normal human peripheral blood mononuclear cells (PBMC). Microarray, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the difference of gene and protein expressions of Molt-4 cells after incubation of the cells with TSA. The results showed that TSA could induce Molt-4 apoptosis in dose- and time-dependent manners but spared PBMCs. Microarray analysis showed that after incubation with TSA for 9 h, 310 genes were upregulated and 313 genes were deregulated. These genes regulate the growth, differentiation and survival of cells. Among these genes, STAT5A was down-regulated by 80.4% and MYC was down-regulated by 77.3%. It was concluded that TSA has definite growth-inhibiting and apoptosis-inducing effects on Molt-4 cells in time- and dose-dependent manners, with weak cytotoxic effects on PBMCs at the same time. The mechanism of TSA selectively inducing apoptosis and inhibiting growth may be ascribed to the changes of pro-proliferation genes and anti-apoptosis genes.
Hong
Zhenya
Z
Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. hongzhenya@eyou.com
Han
Zhiqiang
Z
Xiao
Min
M
Yang
Yang
Y
Xia
Xi
X
Zhou
Jianfeng
J
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D046228:Microarray Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D050799:STAT5 Transcription Factor; C012589:trichostatin A