Involvement of caspase family proteases in FPT inhibitor III-induced apoptosis in human ovarian cancer cells.

We have previously demonstrated that a new farnesyltransferase inhibitor, FPT inhibitor III, triggers apoptosis in human ovarian cancer cells. Here, we report that induction of apoptotic cell death in PA-1 ovarian cancer cells by FPT inhibitor III was accompanied by the activation of interleukin-1 #-converting enzyme (ICE)-like proteases, which have recently been renamed as caspases. The caspase inhibitor, ZVAD-FMK, which inhibits a number of caspase family proteases, blocked FPT inhibitor III-induced apoptotic cell death in a dose-dependent manner. Additionally, cleavage of poly(ADP-ribose) polymerase, an identified in vivo substrate for caspase family proteases, in FPT inhibitor III-treated cells was confirmed by immunoblotting. Our results suggest that the caspase family proteases are involved in the induction of apoptosis triggered by FPT inhibitor III.