Equivalent Death of P-Glycoprotein Expressing and Nonexpressing Cells Induced by the Protein Kinase C Inhibitor Staurosporine

• Published in: Biochemical and biophysical research communications Vol. 276; no. 1; pp. 231 - 237
• Main Authors: Tainton, Kellie M., Ruefli, Astrid A., Smyth, Mark J., Johnstone, Ricky W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.09.2000
• Subjects: apoptosis; Apoptosis - drug effects; Apoptosis - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; caspase; chemotherapy; Enzyme Inhibitors - pharmacology; Humans; multidrug resistance; P-glycoprotein; Protein Kinase C - antagonists & inhibitors; staurosporine; Staurosporine - pharmacology; Tumor Cells, Cultured; P-glycoprotein; multidrug resistance; apoptosis; staurosporine; chemotherapy; caspase
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2000.3459

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 inhibit apoptosis induced by a wide array of cell death stimuli that rely on activation of intracellular caspases for full function. We have previously demonstrated that stimuli including drugs such as hexamethylene bisacetamide (HMBA), the cytotoxic lymphocyte granule protein granzyme B, and pore-forming proteins such as perforin, kill P-gp positive cells in a caspase-independent 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 shown 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.