alpha-Toxin of Staphylococcus aureus overcomes acquired cisplatin-resistance in malignant mesothelioma cells.
alpha-Toxin (alpha-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 alpha-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 alpha-toxin and/or cisplatin followed by determination of cell viability, apoptosis, and signaling pathways. P31res cells were more sensitive to alpha-toxin than P31 wt cells due to induction of apoptosis. A low-toxic concentration of alpha-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.
Johansson
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Department of Medical Biosciences, Clinical Chemistry, Umeå University, Building 6M, 2nd Floor, S-901 85 Umeå, Sweden. david.johansson@medbio.umu.se
Johansson
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Behnam-Motlagh
Parviz
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001427:Bacterial Toxins / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006460:Hemolysin Proteins / Q000494:pharmacology*; D006801:Humans; D008654:Mesothelioma; D010997:Pleural Neoplasms; D015398:Signal Transduction; D013211:Staphylococcus aureus
D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; C021091:staphylococcal alpha-toxin; D002945:Cisplatin