Dichloromethane fraction of Citrus grandis induces apoptosis in a human colorectal cancer cell lines via apoptotic signaling pathway

The incidence of colorectal cancer is rapidly growing in Korea, due to increasingly westernized dietary. We investigated the inhibitory effects of Citrus grandis extracts rich in polymethoxylated flavones in colorectal cancer. CGDF treatment changed the ratio of pro-apoptotic and anti-apoptotic Bcl-2 family proteins and generated ROS. CGDF treatment could promote the release of cytochrome c into the cytosol by activating the expression of caspases and decreasing the expression of IAPs. ROS generated by CGDF may initiate upstream signaling in the apoptotic signaling pathway. CGDF treatment inhibited the growth of xenograft tumors in mice. Gut microbiota analysis showed significant intestinal microbial shifts caused by CGDF ingestion, in which SCFA producers, Clostridium_IV, Oscillibacter, and Acetatifactor, were increased, while the number of potentially tumorigenic bacteria Staphylococcus was decreased. Therefore, we suggest that C. grandis peel extract and its fractions promote the mitochondrial apoptotic cascade in human colorectal cells by shifting the gut microbiota.