The Anti-tumor Effects Of Novel Histone Deacetylase Inhibitors

An increasing number of experimental and clinical studies have highlighted the importance of histone deacetylase (HDAC)-mediated-epigenetic processes in the development of tumor. HDACs are a family of enzymes to regulate cellular functions either through deacetylation of histones or nonhistone transcription factors. In this way HDACs are involved in in chromatin remodeling and assembly, DNA repair and recombination and the consequent regulation of gene expression. Recently, numerous studies have recently revealed that histone deacetylases can be tethered mechanistically to the oncogenesis, maintenance and progression of cancer. HDAC inhibitors have been suggested to be good candidates for the treatment of cancer. HDAC inhibitors induce cell cycle and growth arrest, differentiation or apoptosis of malignant cells of both in vitro models and in vivo xenografts. Strikingly, their anticancer efficacy has been clinically substantiated in broad spectrum of neoplasm types from both haematological and solid origins. Therefore, it is very important to develop efficient, high-selective HDAC inhibitors for the treatment of cancer.The present study was designed to examine the anti-tumor effects of two novel HDAC inhibitors6m and6p. Our current study found that both6m and6p exhibited better HDACs inhibition activities than SAHA, and had good antiproliferative activities against breast cancer, meanwhile with low toxicity in normal cells. Both6m and6p induced cell cycle arrest, apoptosis and inhibited the invasion and migration of breast MDA-MB-231cells. In addition to inhibiting the cell invasion of MDA-MB-231, administration of6m in mice suppressed the growth of MDA-MB-231xenografts without significant toxicity. Our findings suggest that6m have therapeutic or adjuvant therapeutic potential for the treatment of human breast cancer.