Hung W C, Chuang L Y
School of Technology for Medical Sciences, Kaohsiung Medical College, No. 100, Kaohsiung 807, Taiwan, ROC.
Int J Oncol. 1998 Jun;12(6):1339-42. doi: 10.3892/ijo.12.6.1339.
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.
我们之前已经证明，一种新型法尼基转移酶抑制剂——FPT抑制剂III，可引发人卵巢癌细胞的凋亡。在此，我们报告，FPT抑制剂III诱导PA-1卵巢癌细胞发生凋亡性细胞死亡的过程伴随着白细胞介素-1β转换酶（ICE）样蛋白酶的激活，这些蛋白酶最近被重新命名为半胱天冬酶。半胱天冬酶抑制剂ZVAD-FMK可抑制多种半胱天冬酶家族蛋白酶，它以剂量依赖的方式阻断FPT抑制剂III诱导的凋亡性细胞死亡。此外，通过免疫印迹法证实了在FPT抑制剂III处理的细胞中，聚（ADP-核糖）聚合酶（一种已确定的半胱天冬酶家族蛋白酶的体内底物）发生了切割。我们的结果表明，半胱天冬酶家族蛋白酶参与了由FPT抑制剂III触发的凋亡诱导过程。
