Preliminary Study. Histone Deacetylase Inhibitor Tsa Induced In Molt-4 Cell Apoptosis Mechanism

Purpose: Previous observations have validated histone deacetylase inhibitors as promising anti-cancer agents. Despite being therapeutically attractive, the anti-cancer actions of histone deacetylase inhibitors are poorly understood. We sought to understand the mechanism of cell cycle arrest and apoptosis induced by TSA, a typical histone deacetylase inhibitor, in human acute lymphoblastic cell line MOLT-4 by comparing the global gene expression profiles before and after TSA treatment of MOLT-4.Materials and Methods: Kinetics of Cell cycle arrest and apoptotic response were analyzed by flow cytometry. Total RNA was isolated from MOLT-4 cell before and after treatment of TSA under experimental conditions whereby profound apoptotic response is initiated. The total RNA was checked for quality control and subjected to microarray analysis. Some of the microarray data were validated by RT-PCR confirmation.Results: The present microarray detected expression of more than 900 genes was altered with 477 genes up-regulated and 475 down-regulated. Some of microarray data were further confirmed by RT-PCR with good consistence.Conclusions: The mechanism of cell cycle arrest and apoptosis of MOLT-4 induced by TSA involved multiple genes. Most of genes indentified are responsible for regulation of cycle arrest or apoptosis.