Novel Combinations of Foods Targeting Prostate Cancer Prevention

描述（由申请人提供）：前列腺癌（PCa）是美国男性癌症死亡的第二大原因，每年的治疗费用估计接近80亿美元。对生物活性和功能性食品的研究越来越多，推动了前列腺健康食品和膳食补充剂的开发和销售，包括大豆和番茄植物化学物质，男性可能会食用这些产品的组合。然而，不能假设补充剂和功能性食品的组合会更有效，重要的是要确定可能改变饮食干预的有效性或安全性的相互作用。拟议研究的长期目标是定量定义和理解食用大豆或番茄制品可能降低前列腺癌风险的机制。本研究的目的是研究大豆胚芽和/或番茄粉对转基因小鼠前列腺腺癌（TRAMP）模型中前列腺癌进展的影响。同时，我们将研究番茄和大豆胚芽一起食用时番茄类胡萝卜素和大豆异黄酮的生物利用度。为了回答本提案中提出的问题，将在青春期前和癌变过程中给TRAMP小鼠喂食含有2%大豆胚芽和/或10%番茄粉的饲料。本研究的具体目的是：1)研究含番茄和/或大豆胚芽饲料对TRAMP小鼠前列腺癌变进程的影响，并确定其抗癌作用机制；2)测定番茄类胡萝卜素和大豆胚芽异黄酮在TRAMP小鼠体内的生物利用度。据推测，食用大豆胚芽或番茄会降低低分化癌的发病率，两者结合食用的效果不如单独食用。我们将通过cancer pathway findway PCR和免疫组化研究饮食干预的潜在抗癌机制。假设大豆胚芽与番茄之间的相互作用改变了生物活性的生物利用度。将测量类胡萝卜素的生物积累、血清番茄红素代谢物和尿异黄酮，以确定联合食用是否会改变这些生物活性物质的生物利用度，以及这种改变是否与大豆胚芽和/或番茄粉调节前列腺癌的方式有关。提出的研究是了解饮食干预预防前列腺癌功效的独特方法。我们将使用天然食物而不是分离的生物活性物质并研究食物的组合以确定潜在的相互作用。通过更好地了解饮食干预作为预防前列腺癌的替代策略的安全性和有效性，这项研究将使补充剂的消费者和科学界受益。

DESCRIPTION (provided by applicant): Prostate cancer (PCa) is the second leading cause of cancer deaths in men in the U.S. with yearly treatment costs estimated to be near $8 billion. The increasing amount of research on bioactives and functional foods has fueled the development and marketing of foods and dietary supplements for prostate health, including both soy and tomato phytochemicals, and men may consume combinations of these products. However, it can't be assumed that combinations of supplements and functional foods will be more effective, and it is important to identify interactions that could alter the efficacy or safety of dietary interventions. The long range goal of the proposed research is to quantitatively define and understand the mechanisms by which consumption of soy or tomato products may reduce the risk of PCa. The objective of this application is to investigate the effects of soy germ and/or tomato powder containing diets on the progression of PCa in a transgenic adenocarcinoma of mouse prostate (TRAMP) model. In parallel, we will investigate the bioavailability of tomato carotenoids and soy isoflavones when tomato and soy germ are consumed together. To answer the questions raised in this proposal, diets containing 2% soy germ and/or 10% tomato powder will be fed to TRAMP mice prior to puberty and throughout progression of carcinogenesis. The specific aims for this proposal are 1) To investigate the effects of tomato and/or soy germ containing diets on progression of prostate carcinogenesis and identify their anticarcinogenic mechanisms of action in TRAMP mice 2) To measure bioavailability of tomato carotenoids and soy germ isoflavones in TRAMP mice. It is hypothesized that consumption of soy germ or tomato will reduce the incidence of poorly-differentiated carcinoma, and the combination of the two will not be as effective as when consumed individually. Potential anticarcinogenic mechanisms of the dietary interventions will be investigated through cancer pathway findway PCR arrays and immunohistochemistry. It is hypothesized that an interaction between soy germ and tomato alters bioactive bioavailability. Carotenoid bioaccumulation, serum lycopene metabolites, and urinary isoflavones will be measured to determine if combined consumption alters bioavailability of these bioactives and if the alteration correlates with how soy germ and/or tomato powder modulate prostate carcinogenesis. The proposed research is a unique approach to understand the efficacy of dietary interventions for PCa prevention. We will use whole foods rather than isolated bioactives and investigate a combination of foods to identify potential interactions. The research will benefit both consumers of supplements and the scientific community by providing a better understanding of the safety and efficacy of dietary interventions as alternative strategies for PCa prevention.