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.
Hung
W C
WC
School of Technology for Medical Sciences, Kaohsiung Medical College, No. 100, Kaohsiung 807, Taiwan, ROC.
Chuang
L Y
LY
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors; D000590:Amino Acid Chloromethyl Ketones / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D003546:Cysteine Endopeptidases / Q000187:drug effects / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D005260:Female; D006801:Humans; D006868:Hydrolysis; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D011065:Poly(ADP-ribose) Polymerases; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D003546:Cysteine Endopeptidases