Staurosporine and conventional anticancer drugs induce overlapping, yet distinct pathways of apoptosis and caspase activation

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