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Unspecific activation of caspases during the induction of apoptosis by didemnin B in human cell lines
Author(s) -
Johnson Karina L.,
Grubb David R.,
Lawen Alfons
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990201)72:2<269::aid-jcb11>3.0.co;2-d
Subject(s) - apoptosis , caspase , microbiology and biotechnology , cell culture , chemistry , programmed cell death , biology , biochemistry , genetics
Caspases have been implicated in the induction of apoptosis in most systems studied. The importance of caspases for apoptosis was further investigated using the system of didemnin B‐induced apoptosis. We found that benzyloxycarbonyl‐VAD‐fluoromethylketone, a general caspase inhibitor, inhibits didemnin B‐induced apoptosis in HL‐60 and Daudi cells. Acetyl‐YVAD‐chloromethylketone, a caspase‐1‐like activity inhibitor, inhibits didemnin B‐induced apoptosis in Daudi cells, whereas the caspase‐3‐like activity inhibitor, acetyl‐DEVD‐aldehyde, has no effect. Using immunoblots to investigate cleavage of caspases‐1 and ‐3, we found that both caspases are activated in both cell lines. We showed that the caspase substrate poly(ADP‐ribose)polymerase is cleaved in these cells after didemnin B treatment. In both cell lines, poly(ADP‐ribose)polymerase cleavage is inhibited by benzyloxycarbonyl‐VAD‐fluoromethylketone and also by acetyl‐YVAD‐chloromethylketone in Daudi cells. These results indicate that a caspase(s) other than caspase‐3 is required for didemnin B‐induced apoptosis. We show that caspases may be activated during apoptosis that are not required for the progression of apoptosis. J. Cell. Biochem. 72:269–278, 1999. © 1999 Wiley‐Liss, Inc.