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

描述(由申请人提供)：本R21提案是对编号为PA-10-088的项目公告的响应，该项目公告名为“涉及生物活性食品成分的分子靶标的探索性癌症预防研究”。研究表明，食用豆类食品对多种癌症有不同程度的抑制作用。在美国，结肠癌是癌症死亡的常见原因。饮食和生活方式因素，包括肥胖和缺乏体育活动，被认为与结肠癌风险增加有关。大量对人类的观察性研究表明，在某些国家大量食用异黄酮类或大豆与降低结肠癌风险有关。然而，大豆中的异黄酮类化合物对健康有积极作用的证据并不一致。需要进行严格的机理研究来阐明大豆化合物抗结肠癌和其他癌症的细胞靶点和作用机制。我们建议将蛋白质结构和功能的分析与先进的数据管理和药物筛选方法相结合，以确定三种异黄酮类大豆化合物的潜在靶蛋白。我们将利用超级计算机技术，结合分子生物学、细胞培养模型和体内小鼠模型，测试和验证计算机对大豆苷元及其三种代谢物分子靶点(S)的预测。

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.