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。对生物活性物质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，男性可能会消费这些产品的组合。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了解大豆或番茄制品消费可能降低PCa风险的机制。本申请的目的是研究含有大豆胚芽和/或番茄粉的饮食对转基因小鼠前列腺腺癌（TRAMP）模型中PCa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，将在青春期前和整个致癌过程中向TRAMP小鼠饲喂含有2%大豆胚芽和/或10%番茄粉的饲料。该提案的具体目的是1）研究含有番茄和/或大豆胚芽的饮食对前列腺癌发生进展的影响，并确定其在TRAMP小鼠中的抗癌作用机制2）测量番茄类胡萝卜素和大豆胚芽异黄酮在TRAMP小鼠中的生物利用度。据推测，食用大豆胚芽或番茄将降低低分化癌的发病率，两者的组合将不如单独食用时有效。饮食干预的潜在抗癌机制将通过癌症通路findway PCR阵列和免疫组织化学进行研究。据推测，大豆胚芽和番茄之间的相互作用改变生物活性的生物利用度。将测量类胡萝卜素生物累积、血清番茄红素代谢物和尿中的维生素E，以确定联合食用是否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/或番茄粉如何调节前列腺癌发生有关。拟议的研究是了解饮食干预预防PCa的有效性的独特方法。我们将使用完整的食物，而不是孤立的生物活性物质，并研究食物的组合，以确定潜在的相互作用。这项研究将使补充剂的消费者和科学界受益，更好地了解饮食干预作为预防PCa的替代策略的安全性和有效性。 公共卫生相关性：利用饮食方法来降低风险或延迟前列腺癌（PCa）的发病将对公共卫生和医疗保健成本产生深远的影响。拟议的研究将调查膳食大豆胚芽和/或番茄预防PCa的功效，可能确定安全和具有成本效益的预防策略。

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. PUBLIC HEALTH RELEVANCE: Utilizing dietary approaches to reduce the risk or delay the onset of prostate cancer (PCa) would have a profound impact on public health and health care costs. The proposed research will investigate the efficacy of dietary soy germ and/or tomato for prevention of PCa, potentially identifying safe and cost-effective prevention strategies.