Combination of a novel HDAC inhibitor OBP-801/YM753 and a PI3K inhibitor LY294002 synergistically induces apoptosis in human endometrial carcinoma cells due to increase of Bim with accumulation of ROS.
A mass of research have demonstrated that epigenetic gene modulation has been postulated to be an essential mechanism in cancer development and metastasis (Nelson et al., 2012). The modification of histone acetylation plays a critical role in epigenetics as the hotspot of international research (Sriraksa et al., 2013). Especially in histone tails the reversible acetylation of lysine residues has been a key part of activation and repression in transcriptional. The state of histone acetylation is balanced by the opposing activities of histone acetyltransferase (HATs) and histone deacetylase (HDACs) that induces the regulation of post-translational modifications (Hoshino et al., 2010; Duo et al., 2013). Enhanced HDAC activity represses transcriptional of many genes related to differentiation and tumor suppressor genes in cancer cells. Thus, the increased activity of HAT (or HDAC inhibition) promotes gene expression (Hoshino et al., 2007; Ellis et al., 2008),