Apoptosis can be induced by various stimuli including
DNA-damaging anticancer drugs and the
protein kinase inhibitor staurosporine. It is generally believed that the molecular events during execution of apoptosis are shared, as both anticancer drugs and
staurosporine derivatives induce mitochondrial damage,
cytochrome c release and the activation of the
caspase-9 proteolytic cascade. In the present study we show that overexpression of a dominant-negative
caspase-9 mutant abolished the activation of endogenous
caspase-9,
caspase-3 and the cleavage of the
caspase substrate Bid in response to anticancer
drug treatment. Surprisingly, however, only marginal effects were observed during
staurosporine-induced apoptosis. Furthermore, we describe a Jurkat T-cell clone that is completely resistant towards different anticancer drugs, but remains sensitive towards
staurosporine-induced apoptosis. In these cells only
staurosporine, but neither anti-CD95 nor anticancer drugs were able to trigger
caspase activity and the cleavage of
caspase substrates. Our results therefore suggest that the mechanism of
staurosporine-induced apoptosis is more complex and at least partially differs from anticancer
drug-induced
caspase activation. These distinct features of
staurosporine may allow to bypass chemoresistance of
tumor cells and may encourage further clinical trials for the use of
staurosporine derivatives in antitumor
therapy.