Capsaicin enhances the pro‐apoptotic activity of Camptothecin in human small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is characterized by early dissemination, aggressive clinical course and a dismal survival rate. The first line therapy for SCLC patients is cisplatin‐based combination chemotherapy along with radiation. Initially, cisplatin shows excellent results causing remission in 60–80% of the SCLC patients but within a year the tumor inevitably relapses and this relapsed tumor is resistant to cisplatin. A subset of SCLC tumors are unresponsive to cisplatin from the outset. These patients are said to have platinum‐refractory SCLC tumors. Patients with platinum resistant or refractory disease have very limited options, as the only standard chemotherapy with an FDA‐approved drug, camptothecin (and its derivations), 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 enhance the pro‐apoptotic activity of camptothecin in human SCLC. The present study tests the hypothesis that capsaicin can sensitize human SCLC cells to the apoptotic effects of camptothecin. Caspase‐3 activity assays reveal that the combination of camptothecin and capsaicin displayed greater apoptotic activity than the drugs used alone. We verified these results using a second apoptosis assay, namely the Cell Death ELISA and obtained similar results. Chou‐Talalay isobologram analysis showed the interaction between camptothecin and capsaicin is synergistic. Chicken chorioallantoic membrane (CAM) assays confirmed the combinatorial apoptotic effects of capsaicin and camptothecin in human SCLC. The co‐operative effects of capsaicin and camptothecin were also confirmed in human SCLCs xenografted on athymic mice. The results of our experiments pave the way to novel combination therapies for human small cell lung cancer.Support or Funding InformationSupport or Funding Information Funding for our study was supported by a NIH R15‐AREA Grant (2R15CA161491‐02). Furthermore, this study was supported in part by a Center for Natural Products pilot grant from Institutional Development Award (IDeA) Grant number P20GM104932 from the National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH).