Abstract A013: Metabolomics of acute vs. chronic spinach intake in an Apc-mutant genetic background: linoleate and butanoate metabolites targeting HDAC activity and IFN-γ signaling
Authors: Chen Ying-Shiuan , Li Jia , Neja Sultan , Menon Rani , Jayaraman Arul , Lee Kyongbum , Dashwood Wan Mohaiza , Wang Shan , Kapoor Sabeeta , Rajendran Praveen , Zhang Ke , Dashwood Roderick 
Published: December 2022

Abstract
There 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 differential roles of the metabolites in targeting Wnt/b-catenin signaling were recently reported (2). 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 a-diversity of the gut microbiome (3). 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 in cell-based assays and in vivo implicated the linoleate and butanoate metabolites in targeting histone deacetylase (HDAC) activity and the interferon-g (IFN-g) signaling axis. 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).
References
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Citation Format: Ying-Shiuan Chen, Jia Li, Sultan Neja, Rani Menon, Arul Jayaraman, Kyongbum Lee, Wan Mohaiza Dashwood, Shan Wang, Sabeeta Kapoor, Praveen Rajendran, Ke Zhang, Roderick Dashwood. Metabolomics of acute vs. chronic spinach intake in an Apc-mutant genetic background: linoleate and butanoate metabolites targeting HDAC activity and IFN-γ signaling [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A013.