P-glycoprotein protects leukemia cells against caspase-dependent, but not caspase-independent, cell death

Abstract

A major problem with treating patients with cancer by traditional chemotherapeutic regimes is that their tumors often develop a multidrug resistant (MDR) phenotype and subsequently become insensitive to a range of different chemotoxic drugs. One cause of MDR is overexpression of the drug- effluxing protein, P-glycoprotein. It is now apparent that P-glycoprotein may also possess a more generic anti-apoptotic function that protects P- glycoprotein-expressing cancer cells and normal cells from cell death. Herein we show that cells induced to express P-glycoprotein either by drug selection or by retroviral gene transduction with MDR1 cDNA are resistant to cell death induced by a wide range of de..