Tea Modulation of Colon Carcinogenesis

描述（由申请人提供）：绿茶和红茶共同代表了世界上最常消费的饮料，是具有广泛化学预防作用的植物化学物质的极少数来源之一。这种活性和无毒性使茶成为降低人类癌症风险的潜在用途。饮用绿茶可以降低患肺癌、胃癌和胰腺癌等多种癌症的风险。最近有研究表明，在美国人群中，习惯性喝茶与降低患结肠癌的风险有关。然而，在我们完全了解茶的癌症化学预防活动以及茶在人类癌症预防中的可能应用之前，还需要进行更多的研究。这个项目的总体目标是通过阐明茶和癌症预防的机制和识别所涉及的有效成分。使用Apc Min/+结肠癌小鼠动物模型及相关细胞系。该项目将开发有用的生物标志物、新制剂（活性成分的代谢物或类似物）和有效的剂型，以预防人类癌症。具体来说，我们打算验证口服茶是一种有效的致癌抑制剂的假设。以Min小鼠和偶氮氧甲烷（AOM）处理的Min小鼠为动物模型，对茶对异常隐窝灶和结肠肿瘤形成的影响进行剂量反应研究。将评估绿茶和红茶之间可能存在的差异以及咖啡因对结肠肿瘤发生的影响。接下来我们将确定绿茶和红茶对结肠细胞增殖和凋亡的影响并将其与肿瘤发生结果联系起来。为了研究其分子机制，我们将测试茶对Min小鼠结肠中ap - 1、ERK、JNK、c-Jun、j3-catenin等蛋白的调节能力。为了阐明绿茶和红茶在Min和AOMIMin小鼠模型中抑制结肠旋转发生的机制基础，我们将对结肠样品进行花生四烯酸代谢、环氧合酶（COX）蛋白和mRNA水平以及COX、脂氧合酶和磷脂酶A2活性的研究。此外，还将进行茶多酚对COX-2高水平表达的人类结肠腺癌细胞生长的影响的研究。

DESCRIPTION (provided by applicant): Green and black tea together represent the most commonly consumed beverages worldwide and is one of very few sources of phytochemicals with a broad chemopreventive activity against carcinogenesis. This activity and the lack of toxicity make tea an attractive agent for potential use in the reduction of human cancer risk. Consumption of green tea reduces risk for several cancers including lung, stomach, and pancreatic cancer. Recently it has been shown that habitual consumption of tea is associated with a reduced risk for colon cancer in a U.S. population. Nevertheless, much more research is needed before we can fully understand the cancer chemopreventive activities of tea and the possible application of tea in human cancer prevention. The overall goal of this project is to understand tea and cancer prevention by elucidating the mechanisms and identifying the active components involved. The Apc Min/+ mouse animal model for colon cancer and related cell lines will be used. This project will develop useful biomarkers, new agents (metabolites or analogs of the active components), and effective dosage forms for the prevention of human cancer. Specifically, we intend to test the hypothesis that orally administered tea is an effective inhibitor of carcinogenesis. The Min mouse and azoxymethane (AOM)-treated Min mouse will be used as the animal models to conduct dose-response studies for the effect of tea on aberrant crypt foci and colon tumor formation. Possible differences between green tea and black tea and the effect of caffeine on colon tumorigenesis will be assessed. We next will determine the effect of green tea and black tea on the proliferation and apoptosis of cells in the colon and correlate it with the tumorigenesis results. To study the molecular mechanisms, tea will be tested for its ability to modulate AP-l, ERK, JNK, c-Jun, j3-catenin and other proteins in the colons of Min mice. To elucidate the mechanistic basis for the inhibition of colon turnorigenesis by green tea and black tea in the Min and AOMIMin mouse models studies on arachidonic acid metabolism, cyclooxygenase (COX) protein and mRNA levels, and activities of COX, lipoxygenase, and phospholipase A2 will be conducted with colon samples. Furthermore, studies examining the effect of tea polyphenols on the growth of human colon adenocarcinoma cells that have high levels of COX-2 expression will be conducted.