Anti-Tumorigenic Effects of Capsaicin in Colon Cancer

Abstract

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 Apc Min+/ 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 Apc Min+/ 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 dose-and 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.

Chemoprevention of Colorectal Cancer by Dietary Compounds

“…Capsaicin is a promising natural agent in CRC therapy as various favorable effects on different CRC cell lines have been reported regarding the capacity of capsaicin to suppress tumor cell expansion [146,147,148,149]. However, in vitro capsaicin administrated doses need to be tightly adjusted since low concentrations of capsaicin promote metastasis by interfering with key molecules involved in the metastatic cascade.…”

Pharmacological Properties and Health Benefits of Capsicum Species: A Comprehensive Review

“…As a consequence of the undesirable properties and side effects of synthetic drugs, natural products have become increasingly popular over the past few decades. Capsaicin, the spicy ingredient of hot chili peppers, exhibits anti-neoplastic activity in a vast number of cancers like pancreatic cancer, colon cancer, liver cancer, lung cancer, prostate cancer, breast cancer, bladder cancer, and skin cancer [28][29][30][31][32][33][34][35][36]. The significant anticancer capacity of capsaicin targets multiple signaling pathways and cancer-associated genes in different phases of tumor development, including initiation, promotion, progression, and metastasis [37].…”

Potential proapoptotic phytochemical agents for the treatment and prevention of colorectal cancer (Review)

“…Capsaicin is a major pungent component in hot red pepper (79). Capsaicin induces apoptosis in colon cancer cells by arresting the cell cycle at the G 0 /G 1 phase and is associated with an upregulation of the pro-apoptotic protein Bax in conjunction with PARP cleavage (79,80).…”

“…Capsaicin is a major pungent component in hot red pepper (79). Capsaicin induces apoptosis in colon cancer cells by arresting the cell cycle at the G 0 /G 1 phase and is associated with an upregulation of the pro-apoptotic protein Bax in conjunction with PARP cleavage (79,80). Capsaicin alters important cell cycle proteins, including decreasing the expression of cyclin D1 (129) and increasing the expression of p21 (80).…”