P-glycoprotein does not protect cells against cytolysis induced by pore-forming proteins

P-glycoprotein (P-gp) is an ATP-dependent drug pump that confers multidrug resistance (MDR), In addition to its ability to efflux toxins, P-gp can als o inhibit apoptosis induced by a wide array of cell death stimuli that rely on activation of intracellular caspases for full function. We therefore hy pothesized that P-gp may have additional functions in addition to its role in effluxing xenotoxins that could provide protection to tumor cells agains t a host response. There have been a number of contradictory reports concer ning the role of P-gp in regulating complement activation. Given the dispar ate results obtained by different laboratories and our published results de monstrating that P-gp does not affect cell death induced by another membran olytic protein, perforin, we decided to assess the role of P-gp in regulati ng cell lysis induced by a number of different pore-forming proteins. Testi ng a variety of different P-gp-expressing MDR cell lines produced following exposure of cells to chemotherapeutic agents or by retroviral gene transdu ction in the complete absence of any drug selection, we found no difference in sensitivity of P-gp(+ve) or P-gp(-ve) cells to the pore-forming protein s complement, perforin, or pneumolysin. Based on these results, we conclude that P-gp does not affect cell lysis induced by pore-forming proteins.