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

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 an 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 proapoptotic activity of was mediated by the intracellular calcium and calpain pathway. The treatment of human SCLC cells with capsaicin induced increased the activity of calpain 1 and 2 by three-fold 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.

TRPV4: an exciting new target to promote alveolocapillary barrier function

“…TRPV5 and TRPV6 expression is only now just being considered in the lung, and reduced expression of both channels has been noted in human tumor tissues from non-small cell lung cancer patients; this reduced expression is associated with decreased median survival after surgical resection (11). This effect may be related to a role for TRPV6 in facilitating apoptosis, which has been reported for small cell lung cancer cells (29).…”

Anticancer Activity of Herbo-Mineral Formulation in Vitro: A Preliminary Study

“…[22] Capsaicin has also induced apoptosis in human small cell lung cancer cells via the TRPV6 receptor and the calpain pathway. [23] Previous studies suggests, the leaf extract of Moringa oleifera greatly induced apoptosis, inhibited tumor cell growth, and lowered the level of reactive oxygen species (ROS) in human lung cancer cells A549 and MCF-7 cells. [24] Aqueous leaf extract of Moringa oleifera increases the sensitivity of chemotherapy in pancreatic panc-1 cancer cells by downregulation of nuclear factor-kappaB.…”

Anti-Cancer Effects and Mechanisms of Capsaicin in Chili Peppers

“…It is the most aggressive form of lung cancer, with an overall 5-year survival time of less than 5% [40]. The identification of dietary compounds that can decrease the growth of small cell lung cancer could foster the hope of novel therapies for this disease [41]. Recent report from Lau's group suggested that capsaicin induces apoptosis of human small cell lung cancer cells through the TRPV6 and downstream calpain pathway, which revealed TRPV6 might be a useful molecular target for the treatment of human small cell lung cancer [41].…”