Anti-Tumorigenic Effects of Capsaicin in Colon Cancer

Colon cancer is one of most common malignancies in the world. Capsaicin is a major component of chili peppers and has been shown to possess anti-cancer activity against various types of cancers. There is currently a limited number of preclinical studies that test the anti-cancer effects of capsaicin in colon cancer. The first objective of the present study is to investigate whether capsaicin influences tumor formation using a colon cancer mouse model. The second objective is to elucidate the anti-cancer mechanism of capsaicin using an in vitro cell culture system. For the in vivo study, we treated ApcMin+/ mice having truncated deletion of APC (adenomatous polyposis coli) with capsaicin. For the in vitro study, we exposed human colorectal cancer cell lines to different concentrations of capsaicin and performed western blot analysis. Oral gavage of capsaicin at a dose of 20 mg/ kg body weight for 4 weeks tended to decrease the number of polyps (43.5 ± 14.6 vs 27.8 ± 8.8, p = 0.114) and tumor load (78.6 ± 20.9 vs 47.4 ± 21.3, p = 0.083) in the intestine of ApcMin+/ mice. In vitro studies showed that, in human colon cancer cells, capsaicin induced phosphorylation of cyclin D1 at threonine 286 (T286) and decreased cyclin D1 expression in a doseand time-dependent manner. In addition, capsaicin treatment increased intracellular ubiquitination of proteins in a dose-dependent manner and decreased the caspase-like activity of 20S proteasome significantly (p = 0.026). This study identifies capsaicin as a potential anti-cancer agent that targets cyclin D1 degradation and proteasome activity in colon cancer.