Abstract
Metabolite profiling using liquid chromatography-time-of-flight MS was undertaken to identify candidate metabolic processes that account for dry bean effects on disease risk with a specific focus on the development of breast cancer. Normal mammary gland and mammary carcinomas from previously reported experiments were evaluated. Principal component analysis (PCA) of mass spectral data revealed that tissue of both types from control-fed v. bean-fed rats could be distinguished by their metabolomic profiles. Candidate ion identification using MassTRIX analysis software revealed that alterations in eicosanoid, fatty acid, TAG and steroid metabolism partially accounted for the differences observed in both PCA. In addition, evidence was obtained consistent with the hypothesis that the varying inhibitory effects on mammary carcinogenesis of genetically distinct dry bean types were mirrored by differential patterns of lipid metabolites in mammary carcinoma. The use of MassTRIX provided links for metabolite profile enrichment with metabolic pathways in the Kyoto Encyclopedia of Genes and Genomes. Implicated pathways included a linkage between diacylglycerol and protein kinase C and eicosanoid metabolites and inducible cyclo-oxygenase-2 and/or eicosanoid degradation mediated via 15-PG dehydrogenase. These pathways have been reported to be misregulated during the development of cancer. The differences observed between control-fed and bean-fed rats in lipid metabolism require validation using targeted analytical methods and detailed analyses of how bean bioactive food components regulate genes that control lipid biosynthesis, interconversion and catabolism.
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