Abstract 5815: Metabolomics in an Apc-mutant genetic background: Mechanistic insights from acute vs. chronic spinach intake
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AbstractThere is growing interest in the crosstalk between the gut microbiome, metabolomic features, and disease pathogenesis. Colorectal cancer is a major health burden worldwide, linked in part to modifiable risk factors associated with diet and lifestyle (1). The current investigation compared long-term (26 week) and acute (3 day) dietary spinach intake in a genetic model of colorectal cancer. Metabolomic analyses in the polyposis in rat colon (Pirc) model and in wildtype animals corroborated key contributions to anticancer outcomes by spinach-derived linoleate bioactives and a butanoate metabolite linked to increased -diversity of the gut microbiome (2). Combining linoleate and butanoate metabolites in human colon cancer cells revealed enhanced apoptosis and reduced cell viability, paralleling the apoptosis induction observed in colon tumors from rats given long-term spinach treatment. Mechanistic studies indicated reactivation of immune-associated major histocompatibility complex genes in cell-based assays and in vivo, plus differential roles of the metabolites in targeting Wnt/-catenin signaling (3). Clinical translation of the findings from this investigation to at-risk patients might provide valuable quality-of-life benefits by delaying surgical interventions and drug therapies with adverse side effects (4,5).References1.Xi, Y., Xu, P. Global colorectal cancer burden in 2020 and projections to 2040. Transl Oncol 2021;14: 1011741.Chen, Y.-S. et al. Dietary spinach reshapes the gut microbiome in an Apc-mutant genetic background: mechanistic insights from integrated multi-omics. Gut Microbes 2021;13:1972756. 1.Liu, F. et al. Suppression of membranous LPR5 recycling, Wnt/-catenin signaling, and colon carcinogenesis by 15-LOX-1 peroxidation of linoleic acid in PI3P. Cell Rep 2020;32:108049.1.Ulusan, A.M. et al. Optimization of erlotinib plus sulindac dosing regimens for intestinal cancer prevention in an Apc-mutant model of Familial Adenomatous Polyposis (FAP). Cancer Prev Res (Phila) 2021;14:325-336.1.Samadder, N.J. et al. Association of sulindac and erlotinib vs placebo with colorectal neoplasia in Familial Adenomatous Polyposis: secondary analysis of a randomized clinical trial. JAMA Oncol 2018:4:671-677.Citation Format: Sultan Neja, Roderick H. Dashwood. Metabolomics in an Apc-mutant genetic background: Mechanistic insights from acute vs. chronic spinach intake [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5815.
