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.