Serine proteases in histone deacetylase inhibitor-induced apoptosis.

tivatin In an elicite obser induc trigge butyr toxic dition 10 da seeme prote rather If th TSA o idea We fo itory tion u inhibi with tone deacetylase inhibitors (HDACi) are a new of targeted antitumor agents (1). They exert their y against cancer cells by stimulating differentiation, ibiting proliferation, and by inducing apoptosis. ugh the latter has been extensively studied, our rstanding of how HDACi harness the apoptotic nery is incomplete. In particular, the significance of ses and other proteases in the apoptotic pathwaymeby HDACi has not yet been conclusively resolved. cent article, the hydroxamic acidHDACi trichostatin A) and vorinostat [also called suberoylanilide hydroacid (SAHA)] have been reported to induce caspaseendent, but serine protease-dependent, apoptosis in eatic cancer cells (2). It was shown that the serine proinhibitor 4-(2-aminoethyl)-benzenesulfonylfluoride SF; also called Pefabloc; and called ISP in ref. 2) ble to block TSA-induced apoptosis, leading to the sion that the latter depended on serine protease ac[AEBSF functions by sulfonylating the active-site residue in serine proteases (3), but it may also covamodify other proteins (4).] have reservations about this conclusion, because vorinostat-induced, but not NaB-induced, histone hyper-