Combinatorial apoptotic activity of capsaicin and camptothecin in small cell lung cancer

Abstract

Cisplatin‐based chemotherapy is the standard of care for small cell lung cancer. However, one of the challenges with SCLC therapy is that patients quickly become resistant to cisplatin. Patients with platinum resistant or refractory disease have very limited options, as the only standard chemotherapy with an FDA‐approved drug, camptothecin, has an objective response rate of approximately 3% and little or no survival benefit. Such sobering statistics define the arena where there is an urgent need for drugs which may increase the efficacy of camptothecin in platinum resistant disease. The present study tests the hypothesis that capsaicin can sensitize human SCLC cells to the apoptotic effects of cisplatin or camptothecin. Caspase‐3 activity assays reveal that the combination of camptothecin and capsaicin displayed greater apoptotic activity than any of the compounds used alone. We verified these results using a second apoptosis assay and obtained similar results. Chicken chorioallantoic membrane assays confirmed the combinatorial effects of capsaicin and camptothecin. Capsaicin also sensitized cisplatin‐resistant SCLC cells to camptothecin‐induced apoptosis. The synergistic effects of capsaicin and camptothecin are mediated by intracellular calcium and the calpain pathway. Our data foster the hope of novel combination therapies for platinum‐resistant SCLCs.Support or Funding InformationFunding for our study was supported by the an NIH R15‐AREA Grant (1R15HL113681‐01A1) and an AICR Investigator Grant.