The role of caspase-9, bax, and p53 in the apoptotic response triggered by 9-hydroxystearic acid

HDAC1 (Histone deacetylase) activity is inhibited by 9-hydroxystearic acid (9-HSA) (1,2). HDAC1 inhitors specifically induce differentiation/apoptosis of transformed cells in vitro and suppres tumor growth in vivo. 9-HSA, an endogenous lipid peroxidation product, induces apoptosis characterized by mitochondrial stress, but so far the critical elements of these apoptotic program remain poorly defined. To characterize this apoptotic program in more detail we used a human ostesarcoma cell line p53 w.t. and we studied important elements of the apoptotic response such as p53, Bax and caspase 9. We demonstrate that Bax expression level and caspase 9 activity are critical for apoptosis induced by 9-HSA and that the susceptibility to cell death in response to 9-HSA treatment is regulated by p53 acetylation level.