p15INK4b in HDAC inhibitor-induced growth arrest

AbstractHistone deacetylase (HDAC) inhibitors arrest human tumor cells at the G1 phase of the cell cycle and activate the cyclin-dependent kinase inhibitor, p21WAF1/Cip1. However, several studies have suggested the existence of a p21WAF1/Cip1-independent molecular pathway. We report here that HDAC inhibitors, trichostatin A (TSA) and sodium butyrate, activate the p15INK4b gene, a member of the INK4 gene family, through its promoter in HaCaT cells. Furthermore, we show that up-regulation of p15INK4b by TSA is associated with cell growth inhibition of HCT116 p21 (−/−) cells. Our findings suggest that p15INK4b is one of the important molecular targets of HDAC inhibitors