Unspecific activation of caspases during the induction of apoptosis by didemnin B in human cell lines

Karina L. Johnson, David R. Grubb, Alfons Lawen

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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.

Original languageEnglish
Pages (from-to)269-278
Number of pages10
JournalJournal of Cellular Biochemistry
Issue number2
Publication statusPublished - 15 Jan 1999


  • Caspase-1
  • Caspase-3
  • Daudi
  • HL-60
  • Poly(ADP-ribose)polymerase
  • Roscovitine

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