Capsaicin displays anti‐proliferative activity of human small cell lung cancer via recruitment of E2F4 to downstream target genes

Abstract

Capsaicin the pungent ingredient of chili peppers can inhibit the growth of several types of human cancers in both cell culture and animal models. Depending on the nature of the cells, capsaicin induces cell cycle arrest at the G1/S boundary or causes apoptosis. Although, the signaling pathways underlying the apoptotic effects of capsaicin are well studied, very little is known about the molecular mechanisms underlying capsaicin‐induced cell cycle arrest. Our study showed that capsaicin displays anti‐proliferative activity in human small cell lung cancer cells (SCLC). The treatment of human SCLC cells with capsaicin resulted in downregulation of E2F‐responsive S‐phase genes like cdc6, cdc25A and cyclin E. The dietary administration of capsaicin led to reduction in the size of established SCLC tumors in nude mice. Furthermore, capsaicin suppressed tumor growth in CAM assays. The anti‐proliferative effect of capsaicin was mediated via E2F4 and resulted in enhanced recruitment of E2F4 and p130 on E2F‐responsive proliferative promoters, leading to repression of their transcription. Our findings suggest that the anti‐proliferative effects of capsaicin could be useful in the therapy of human SCLCs. Funding for our study was supported by a COBRE Pilot Grant Research, the PhRMA Foundation, an MU‐ADVANCE Fellowship, and the Flight Attendant Medical Research Institute YCSA Grant.