Inhibitory Effect of Garcinol on Obesity-Exacerbated, Colitis-Mediated Colon Carcinogenesis.

Scope Epidemiological studies show a consistent and compelling association between the risk of colorectal cancer development and obesity, but its mechanisms remain poorly understood. Evidence is mounting that colorectal cancer could be prevented by nutritional supplements, such as phytochemicals. Garcinol, a polyisoprenylated benzophenone derivative, is widely present in Garcinia plants. We investigated the potential role of garcinol supplementation in ameliorating obesity-induced colon cancer development. Methods and results An animal model to investigate the effect of high-fat-diet (HFD)-induced obesity on promoting colitis-associated colon cancer (AOM (azoxymethane)/DSS (dextran sodium sulfate)-induced) was designed. The results showed that HFD could promote colitis-associated colon cancer as compared to an AOM/DSS group without the intervention of obesity, and supplementing with 0.05% garcinol in the diet could significantly ameliorate obesity-promoted colon carcinogenesis. The results also revealed that the microbiota composition of each group was significantly different and clustered. The most representative genera were Alistipes, Romboutsia, and Ruminococcus. The RNA-sequencing results showed that the administration of garcinol could regulate genes and improve obesity-promoting colitis-associated colon carcinogenesis. Conclusion Our results suggest that garcinol can prevent obesity-promoted colorectal cancer, and these findings provide important niches for the future development of garcinol as functional foods or adjuvant therapeutic agents. This article is protected by copyright. All rights reserved.