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(Gl)方面具有特殊作用。随着证据支持茶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，作为潜在的防癌药物。然而，茶儿茶素对消化条件的稳定性很差，这表明儿茶素消化产品实际上可能是这种饮料的化学预防活性的部分原因。目前，人们对茶儿茶素的完全消化去向和/或消化对茶癌预防活动的影响知之甚少。由于这一认识上的差距，尚不清楚是土生儿茶素还是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饮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，并确定儿茶素来源的主要消化最终产物的特征，这些产物可能不同于目前被认为是生理活性物质的天然儿茶素。本研究的具体目的是：(1)研究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条件对茶儿茶素谱的影响。利用高效液相色谱质谱联用和MS/MS联用技术，我们将对肠腔中存在的主要茶多酚形式进行表征；(2)确定消化儿茶素修饰对癌症预防活性的影响。将通过体外筛选试验比较天然(未消化)和消化的儿茶素的防癌活性的差异，这些试验的重点是胃和结肠癌细胞的增殖、细胞内的氧化应激(DCF和NFkB活性分析)以及对II相酶活性的调节(即苯醌还原酶)。相关性：我们的研究将确定人类消化对茶儿茶素防癌活性的影响。具有终极生物学意义的茶叶化合物的发现将使未来对特定茶儿茶素形式的实验策略成为可能，这些形式对癌症风险和结果具有积极影响。

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.