p15(INK4b) in HDAC inhibitor-induced growth arrest.

Histone deacetylase (HDAC) inhibitors arrest human tumor cells at the G1 phase of the cell cycle and activate the cyclin-dependent kinase inhibitor, p21(WAF1/Cip1). However, several studies have suggested the existence of a p21(WAF1/Cip1)-independent molecular pathway. We report here that HDAC inhibitors, trichostatin A (TSA) and sodium butyrate, activate the p15(INK4b) gene, a member of the INK4 gene family, through its promoter in HaCaT cells. Furthermore, we show that up-regulation of p15(INK4b) by TSA is associated with cell growth inhibition of HCT116 p21 (-/-) cells. Our findings suggest that p15(INK4b) is one of the important molecular targets of HDAC inhibitors.