Abstract
BackgroundSmall cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays anti-proliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.Methodology/Principal FindingsBrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently suppressed the growth of H69 human SCLC tumors in vivo as ascertained by CAM assays and nude mice models. The second part of our study attempted to provide insight into molecular mechanisms underlying the anti-proliferative activity of capsaicin. We found that the anti-proliferative activity of capsaicin is correlated with a decrease in the expression of E2F-responsive proliferative genes like cyclin E, thymidylate synthase, cdc25A and cdc6, both at mRNA and protein levels. The transcription factor E2F4 mediated the anti-proliferative activity of capsaicin. Ablation of E2F4 levels by siRNA methodology suppressed capsaicin-induced G1 arrest. ChIP assays demonstrated that capsaicin caused the recruitment of E2F4 and p130 on E2F-responsive proliferative promoters, thereby inhibiting cell proliferation.Conclusions/SignificanceOur findings suggest that the anti-proliferative effects of capsaicin could be useful in the therapy of human SCLCs.
Highlights
Small cell lung cancer (SCLC) is an aggressive malignancy representing 13% of all lung cancer cases, with an overall 5-year survival rate of less than 5% [1,2]
Treatment of H69 and H82 human SCLC cells with 50 mM capsaicin can potently suppress the growth of these cells in a time dependent manner, with the maximal growth-inhibitory effect of capsaicin being displayed at 72 hours post treatment (Fig. 1, A)
BrdU assays were used to examine the anti-proliferative effects of capsaicin in four human SCLC cell lines, namely H69, H82, DMS53 and DMS114 [31,48] and two normal lung epithelial cell lines (NHBE and small airway epithelial cells (SAEC))
Summary
Small cell lung cancer (SCLC) is an aggressive malignancy representing 13% of all lung cancer cases, with an overall 5-year survival rate of less than 5% [1,2] Such statistics emphasize the need for novel treatment strategies for this disease. Recent advances in the basic understanding of molecular events involved in SCLC progression have led to the identification of potential agents for therapeutic interventions [2,3,4,5] These strategies include growth factor/receptor-specific inhibitors, protein kinase inhibitors and nutritional agents. Chemoprevention studies demonstrate that capsaicin can suppress carcinogenesis of the skin, colon, lung, tongue and prostate [8,9,10,11,12] These studies have addressed the chemopreventative potential of capsaicin, only a few have addressed its potential as an anti-cancer agent. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
