Equivalent death of P-glycoprotein expressing and nonexpressing cells induced by the protein kinase C inhibitor staurosporine

P-glycoprotein (P-gp) is an ATP-dependent drug pump that confers multidrug resistance. In addition to its ability to efflux toxins P-gp can also inhib it apoptosis induced by a wide array of cell death stimuli that rely on act ivation of intracellular caspases for full function. We have previously dem onstrated that stimuli including drugs such as hexamethylene bisacetamide ( HMBA), the cytotoxic lymphocyte granule protein granzyme B, and pore-formin g proteins such as perforin, kill P-gp positive cells in a caspase-independ ent manner. We therefore hypothesised that drugs that are not effluxed by P -gp and which induce cell death in the absence of caspase activation could induce death of P-gp expressing cells. Staurosporine has been previously sh own to kill cells in the absence of caspase activation. Consistent with our hypothesis, we demonstrate here that staurosporine can equivalently kill P -gp(+ve) and P-gp(-ve) tumor cell lines in a caspase-independent manner. (C ) 2000 Academic Press.