S-Allylcysteine Inhibits PhIP/DSS-Induced Colon Carcinogenesis through Mitigating Inflammation, Targeting Keap1, and Modulating Microbiota Composition in Mice
Journal
Molecular Nutrition and Food Research
Journal Volume
64
Journal Issue
23
Date Issued
2020
Author(s)
Abstract
Scope: The objective of the present study is to investigate whether edible S-allylcysteine (SAC) has chemoprophylactic effects on inflammation-associated colon carcinogenesis induced in mice through 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) exposure and promoted by dextran sodium sulfate (DSS) and whether its cancer-prevention effects are related to the modulation of gut microbiota composition. Methods and results: Dietary administration of 0.05% SAC in mice for 18 weeks prevents shortening of the colon length and reduces the number of colon polyps. The SAC supplementation markedly decreases PhIP/DSS-induced plasma and colon tissue pro-inflammatory cytokines. These changes are accompanied by the suppression of inducible nitric oxide synthase, COX-2, and MMP-2 protein expression in colon tissue. In addition, the dietary administration of SAC increases heme oxygenase-1 expression through activation of the NF-E2-related factor 2 pathway, thus abating PhIP/DSS-induced colitis. The 16S rRNA gene sequence data indicate that SAC counteracted the PhIP/DSS-induced gut dysbiosis, resulting in a microbiota composition similar to the control group. Conclusion: The results indicate that SAC can suppress PhIP/DSS-induced colorectal carcinogenesis. Hence, SAC may merit further clinical investigation as a chemoprevention strategy for retarding colitis-associated colon cancer in humans. ? 2020 Wiley-VCH GmbH
Subjects
2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine; chemoprevention; colorectal cancer; S-allylcysteine
SDGs
Type
journal article