Effect of digestion on the cancer chemopreventative activity of tea catechins

描述（由申请人提供）：饮茶与许多癌症预防活动有关，流行病学证据表明，茶在减少胃肠道癌症方面具有特殊作用。有证据表明茶具有潜在的化学预防作用，研究集中在茶多酚，更具体地说，茶儿茶素，作为潜在的癌症预防剂。然而，众所周知，茶儿茶素对消化条件的稳定性很差，这表明儿茶素消化产物实际上可能是这种饮料的化学预防活性的部分原因。目前，关于茶儿茶素的完全消化命运和/或消化对茶癌预防活动的影响知之甚少。由于这方面的知识差距，目前尚不清楚是否是天然儿茶素或儿茶素消化分解产物对观察到的癌症预防活动最关键。我们的长期目标是确定膳食中植物化学成分的生理相关性。我们的总体目标是确定人类消化对茶儿茶素癌症预防活性的影响，并表征儿茶素来源的主要消化最终产物，这些产物可能不同于目前认为具有生理活性的天然儿茶素。本研究的具体目的是：(1)表征茶儿茶素的消化行为和消化终产物的形成。我们将使用体外消化模型来确定胃和小肠状况对茶儿茶素谱的影响。通过使用HPLC-MS和MS/MS技术，我们将表征存在于肠腔中的主要茶多酚形式；(2)建立消化儿茶素修饰对肿瘤预防活性的影响。天然（未消化）和消化儿茶素的癌症预防活性差异将通过体外筛选试验进行比较，重点是胃癌和结肠癌细胞增殖、细胞内氧化应激（DCF和NFkB活性测定）和II期酶活性（即醌还原酶）的调节。相关性：我们的研究将确定人体消化对茶儿茶素抗癌活性的影响。发现具有最终生物学意义的茶化合物将使未来的实验策略成为可能，以确定对癌症风险和预后有积极影响的特定茶儿茶素形式。

DESCRIPTION (provided by applicant): Consumption of tea is associated with numerous cancer preventative activities and epidemiological evidence suggests a specific role in reducing cancers of the gastrointestinal (Gl) tract. With evidence supporting a potential chemopreventative role for tea, studies have focused on tea polyphenols, and more specifically tea catechins, as potential cancer preventative agents. However, stability of tea catechins to digestive conditions is known to be poor, suggesting that catechin digestive products may actually be responsible, in part, for the chemopreventative activity of this beverage. Currently, very little is known regarding the full digestive fate of tea catechins, and/or the effects of digestion on tea cancer preventative activities. Due to this gap in knowledge, it is unclear whether native catechins or products of catechin digestive breakdown are most critical to observed cancer preventative activities. Our long-term goal is to determine physiological relevance of dietary phytochemical constituents. Our overall objective is to determine the effects of human digestion on tea catechin cancer preventative activity and characterize major digestive end-products of catechin origin that may differ from native catechins currently believed to be physiologically active agents. Specific Aims for this study are: (1) To characterize tea catechin digestive behavior and formation of digestive end-products. We will use an in vitro digestive model to determine effects of gastric and small intestinal conditions on tea catechin profile. By use of HPLC-MS and MS/MS techniques we will characterize major tea polyphenol forms present in the intestinal lumen; (2) To establish the effect of digestive catechin modification on cancer preventative activity. Differences in cancer preventative activity of native (undigested) and digested catechins will be compared by in vitro screening assays focused on gastric and colon cancer cell proliferation, intracellular oxidative stress (DCF and NFkB activity assays), and regulation of Phase II enzyme activity (i.e. quinone reductase). Relevance: Our studies will determine the influence of human digestion on the cancer preventative activities of tea catechins. Discovery of tea compounds which hold ultimate biological significance will enable future experimental strategies for specific tea catechin forms that positively affect cancer risk and outcomes.