Molecular Mechanisms and Targets of Soy Compounds in the Prevention of Colon Canc

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DESCRIPTION (provided by applicant): This R21 proposal is submitted in response to Program Announcement Number PA-10-088 entitled "Exploratory Cancer Prevention Studies Involving Molecular Targets for Bioactive Food Components." Consumption of soy based foods has been shown to exhibit varying degrees of inhibitory effects on numerous types of cancers. Colon cancer is a common cause of cancer death in the United States. Diet and lifestyle factors, including obesity and lack of physical activity, are believed to be associated with increased colon cancer risk. Numerous observational studies in humans have indicated that a high consumption of isoflavones or soy in certain countries is associated with a reduced risk of colon cancer. However, the evidence for positive health effects of the isoflavones in soy is quite inconsistent. Rigorous mechanistic studies are needed to elucidate the cellular targets and mechanisms of action of soy compounds against colon and other cancers. We propose to combine analyses of protein structure and function with advanced methods of data management and drug screening to identify potential target proteins for three isoflavone soy compounds. We will use supercomputer technology combined with molecular biology, cell culture models and an in vivo mouse model to test and validate the computer prediction of the molecular target(s) of daidzein and three of its metabolites.