Dietary Supplementation of Foxtail Millet Ameliorates Colitis-Associated Colorectal Cancer in Mice via Activation of Gut Receptors and Suppression of the STAT3 Pathway

• Published in: Nutrients 2020-08, Vol.12 (8), p.2367
• Main Authors: Zhang, Bowei, Xu, Yingchuan, Liu, Shuang, Lv, Huan, Hu, Yaozhong, Wang, Yaya, Li, Zhi, Wang, Jin, Ji, Xuemeng, Ma, Hui, Wang, Xiaowen, Wang, Shuo
• Format: Article
• Language: English
• Subjects: Activation; Angiogenesis; Animals; aryl hydrocarbon receptor (AHR); Azoxymethane; Basic Helix-Loop-Helix Transcription Factors - metabolism; Cancer; Cell proliferation; Cereals; Colitis; Colitis-Associated Neoplasms - blood; Colitis-Associated Neoplasms - chemically induced; Colitis-Associated Neoplasms - diet therapy; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - blood; Colorectal Neoplasms - chemically induced; Colorectal Neoplasms - diet therapy; Cytokines; Dextran; Dextran Sulfate; Dextrans; Diet; Diet - methods; Dietary fiber; Dietary Supplements; Disease Models, Animal; Disease Progression; Drinking water; foxtail millet; G-protein-coupled receptor (GPCR); Gastrointestinal Microbiome - physiology; Gene expression; grain; Health risks; Indoles; Inflammatory bowel disease; Inflammatory bowel diseases; Interleukin 17; Interleukin 6; Interleukin-17 - blood; Interleukin-6 - blood; Intestine; Laboratory animals; Metabolites; Mice; Mice, Inbred BALB C; Microbiota; Microorganisms; Millet; Mortality; Oryza; Phosphorylation; Phosphorylation - physiology; Receptors, Aryl Hydrocarbon - metabolism; Receptors, G-Protein-Coupled - metabolism; Rice; Risk management; Setaria italica; Setaria Plant; Signal Transduction - physiology; Sodium sulfate; Stat3 protein; STAT3 Transcription Factor; Survival; Tumor necrosis factor-TNF; Tumorigenesis
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12082367

Coarse cereal intake has been reported to be associated with reduced risk of colorectal cancer. However, evidence from intervention studies is absent and the molecular basis of this phenomenon remains largely unexplored. This study sought to investigate the effects of foxtail millet and rice, two common staple grains in Asia, on the progression of colitis-associated colorectal cancer (CAC) and define the mechanism involved. In total, 40 BALB/c mice were randomized into four groups. The Normal and azoxymethane/dextran sodium sulfate (AOM/DSS) groups were supplied with an AIN-93G diet, while the millet- and rice-treated groups were supplied with a modified AIN-93G diet. Compared to the AOM/DSS-induced CAC mice supplemented with rice, an increased survival rate, suppressed tumor burden, and reduced disease activity index were observed in the millet-treated group. The levels of IL-6 and IL-17 were decreased in the millet-treated group compared to both the AOM/DSS and AOM/DSS + rice groups. Millet treatment inhibited the phosphorylation of STAT3 and the related signaling proteins involved in cell proliferation, survival and angiogenesis. These beneficial effects were mediated by the activation of gut receptors AHR and GPCRs via the microbial metabolites (indole derivates and short-chain fatty acids) of foxtail millet. Moreover, millet-treatment increased the abundance of and compared to the rice-treated mice. This study could help researchers to develop better dietary patterns that work against inflammatory bowel disease (IBD) and for CAC patients.