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Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway

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Abstract

Capsaicin, the pungent ingredient of chili peppers, displays potent anti-neoplastic activity in a wide array of human cancer cells. The present manuscript examines the signaling pathways underlying the apoptotic activity of capsaicin in human small cell lung cancer (SCLC) in vitro and in vivo. Studies in neuronal cells show that capsaicin exerts its biological activity via the transient receptor potential vanilloid (TRPV) superfamily of cation-channel receptors. The TRPV family is comprised of six members (TRPV1–6). Capsaicin is a known agonist of the TRPV1 receptor. We observed that capsaicin-induced apoptosis in human SCLC cells was mediated via the TRPV receptor family; however it was independent of TRPV1. Surprisingly, the apoptotic activity of capsaicin required the TRPV6 receptor. Depletion of TRPV6 receptor by siRNA methodology abolished the apoptotic activity of capsaicin in SCLC cells. Immunostaining and ELISA showed that TRPV6 receptor was robustly expressed on human SCLC tissues (from patients) and SCLC cell lines but almost absent in normal lung tissues. This correlates with our results that capsaicin induced very little apoptosis in normal lung epithelial cells. The pro-apoptotic activity of capsaicin was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin increased the activity of calpain 1 and 2 by threefold relative to untreated SCLC cells. Such calpain activation, in response to capsaicin, was downstream of the TRPV6 receptor. Taken together, our data provide insights into the mechanism underlying the apoptotic activity of capsaicin in human SCLCs.

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Acknowledgments

We thank Dr. Srikumar Chellappan and his laboratory for their help and support. This work was supported by the grants Young Clinical Scientist Award (#82115) from the Flight Attendant Medical Association, Miami, FL, the NIH R15 AREA grant (1R15CA161491-01A1) and a AICR research grant to PDG. RGC was the recipient of a summer research fellowship is supported by grants from the West Virginia IDeA Network of Biomedical Research Excellence (P20RR016477 and P20GM103434).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Physiology and Toxicology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    Jamie K. Lau, Kathleen C. Brown, Aaron M. Dom, Brent A. Thornhill, Clayton M. Crabtree, Haley E. Perry, J. Michael Brown, John G. Ball, Rebecca G. Creel, C. Luke Damron, William D. Rollyson, Cathryn D. Stevenson, Monica A. Valentovic & Piyali Dasgupta

  2. Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    Theodore R. Witte & W. Elaine Hardman

  3. Department of Anatomy and Pathology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA

    A. Betts Carpenter

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  1. Jamie K. Lau
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Correspondence to Piyali Dasgupta.

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Lau, J.K., Brown, K.C., Dom, A.M. et al. Capsaicin induces apoptosis in human small cell lung cancer via the TRPV6 receptor and the calpain pathway. Apoptosis 19, 1190–1201 (2014). https://doi.org/10.1007/s10495-014-1007-y

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