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Project Description

Dr. Piyali Dasgupta

Small cell lung cancer (SCLC) is characterized by rapid progression, early metastasis and a dismal survival rate. Chemotherapy remains the cornerstone of treatment for SCLC. However, the acquisition of chemotherapy resistance and subsequent relapse are responsible for the poor treatment outcomes in SCLC patients. Recent studies have shown that capsaicin (the spicy ingredient of chilli peppers) can inhibit the growth of human gliomas, non small cell lung cancers, colon cancers and prostate cancers. The growth-inhibitory abilities of capsaicin have not been studied in human SCLCs. Data obtained in our laboratory indicate that capsaicin displays potent growth-inhibitory activity on multiple human SCLC cell lines. TUNEL and caspase-3 cleavage assays show that capsaicin induced 5-6 fold increase in apoptosis in human SCLC cells. Preliminary experiments in nude mouse models indicate that capsaicin can suppress the growth of human SCLC tumors xenotransplanted in nude mice. Most interestingly, the apoptotic activity of capsaicin was only displayed in SCLC cells and not in normal human lung epithelial cells. Previous literature has established that the bioactivity of capsaicin is mediated by TRPV (transient receptor potential V) receptors on target cells. Although, capsaicin is a TRPV1 agonist, recent studies have demonstrated TRPV1-independent mechanisms of capsaicin action. Immunoblotting experiments showed that TRPV1 receptor is not expressed in human SCLC cells. Instead, the growth-inhibitory activity of capsaicin required the TRPV6 receptor and depletion of TRPV6 by siRNA ablated the growth-inhibitory activity of capsaicin. These studies suggest that capsaicin may have potential applications as a novel nutrition-based therapeutic agent for the treatment of human SCLCs

   

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