Search for novel circulating cancer chemopreventive biomarkers of dietary rice bran intervention in ApcMin mice model of colorectal carcinogenesis, using proteomic and metabolic profiling strategies
journal contributionposted on 15.03.2016 by Leonie Norris, Aditya Malkar, Emma Horner-Glister, Amirmansoor Hakimi, Leong L. Ng, Andreas J. Gescher, Colin Creaser, Stewart Sale, Donald J.L. Jones
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Scope: There is strong epidemiological evidence indicating that consumption by humans of whole-grain foods including rice bran may be associated with a low incidence of cancer, especially in the colorectum. Molecular processes associated with cancer development may be retarded by fiber consumption. Consequently, intervention with dietary fiber might be suitable as a cancer chemoprevention strategy in high-risk populations. Here, we searched for putative molecular mechanism-based efficacy biomarkers of rice fiber consumption in the plasma of mice characterized by a genetic propensity to develop gastrointestinal adenomas. The hypothesis was tested that metabolic and proteomic changes in blood reflect the chemopreventive activity of rice bran. Methods and results: ApcMin mice received diet supplemented with rice bran at 5, 15, and 30%. Blood and tissue samples were taken. Plasma was subjected to MS-based proteomic and metabolic profiling analyses as well as assessment of hematocrit values. Gastrointestinal tracts were removed and adenomas were counted and their size was measured so that total tumor burden could be calculated. The hypothesis was tested that metabolic and proteomic changes in blood reflect chemopreventive activity. Conclusion: Rice bran consumption reduced adenoma burden and number in a dose-related fashion when compared to controls. Metabolic profiling data demonstrated strong clustering of the groups indicating that metabolic pathways are perturbed. Proteomic analysis identified adiponectin as a molecule that was significantly altered, which may play a role in tumor suppression.
The authors would like to thanks the HOPE against Cancer Foundation for funding this study. We also thank RiceBran Technologies (formerly Nutracea, Scottsdale, AR, USA) for generous support of the study. Work was also supported by a Cancer Research UK Programme grant (C325/A13101).