α-Toxin of Staphylococcus aureus overcomes acquired cisplatin-resistance in malignant mesothelioma cells

Abstract

α-Toxin (α-hemolysin) of Staphylococcus aureus is a pore-forming bacterial toxin which after caveolin-1-dependent assembly induces apoptosis in eukaryotic cells. We investigated if a sub-toxic concentration of staphylococcal α-toxin could enhance cisplatin-induced apoptosis and overcome acquired cisplatin-resistance in cultured malignant pleural mesothelioma (MPM) cells. MPM cells (P31wt) and a cisplatin-resistant sub-line (P31res) was incubated with α-toxin and/or cisplatin followed by determination of cell viability, apoptosis, and signaling pathways. P31res cells were more sensitive to α-toxin than P31 wt cells due to induction of apoptosis. A low-toxic concentration of α-toxin re-sensitized cisplatin P31res cytotoxicity by apoptosis-induced through the mitochondrial pathway without detectable activation of common up-stream apoptosis signaling proteins. The toxin/drug combination should be tested for cisplatin-resistant mesothelioma treatment.