Anti-cancer effects by the green tea catechins

绿茶儿茶素的抗癌作用

• 批准号: 6918263
• 负责人: SEUNG Joon BAEK
• 金额: $ 12.45万
• 依托单位: UNIVERSITY OF TENNESSEE KNOXVILLE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-06 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6918263
• 关键词: alternative medicine; antineoplastics; apoptosis; biological products; carcinogenesis inhibitor; cell line; chemoprevention; colorectal neoplasms; flavonoids; gene expression profiling; gene induction /repression; genetic transcription; human genetic material tag; laboratory mouse; nutrition aspect of cancer; nutrition related tag; tea; transcription factor

DESCRIPTION (provided by applicant): There is persuasive epidemiological evidence that consumption of dietary polyphenolic plant-derived compounds reduce chronic disease such as cancer. Many laboratory studies including us have shown the inhibitory effect of dietary compounds including resveratrol, genistein, and diaryl disulfide against carcinogenesis in vivo and in vitro. Green tea and its constituent polyphenols (catechins) have been shown to possess anti-tumor properties in a wide variety of experimental systems. Some reports are suggesting an involvement of p53 tumor suppressor proteins, but others do not. Thus, the exact molecular mechanism by which green tea induce anti-tumorigenic effect is not clear. One promising mechanism is the induction of apoptosis by catechins. Indeed, catechins have been known to be associated with the induction of apoptosis. In this regard, our hypothesis of this novel proposal is that the cancer chemopreventive effect of green tea components including catechin (-) epigallocatechin 3-gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), and epicatechin (EC) is through the induction of apoptotic mechanisms involving the induction of a newly identified TGF-beta superfamily protein, NAG-1 (Nonsteroidal anti-inflammatory drug activated gene). The rationale for this hypothesis is based on the followings: 1) identification of the NAG-1 gene as a dietary induced gene, 2) higher NAG-1 expression in normal colonic epithelial than adjacent tumor cells, 3) NAG-1 has pro-apoptotic and anti-tumorigenic activities reported by us and other groups. Therefore, the overall goal of this project is to identify single catechins or the combinations of catechins for higher NGA-1 inducer in human colorectal cancer cells. To investigate the molecular mechanisms of which a green tea component or combination of them induces NAG-1 expression, we will use two different models, HCT- 116 human colorectal adenocarcinoma cells and mouse model system with following specific aims: 1. Define transcriptional regulatory mechanisms responsible for NAG-1 induction by ECG and other catechins. 2. Profile changes in gene expression following ECG treatment. 3. Compare the preventative and therapeutic efficacy of individual and combination catechins in animal models of colorectal cancer.

描述（由申请人提供）：有令人信服的流行病学证据表明，食用植物源性多酚化合物可以减少癌症等慢性疾病。包括我们在内的许多实验室研究表明，膳食化合物（包括白藜芦醇、染料木黄酮和二芳基二硫化物）在体内和体外具有抗癌作用。绿茶及其成分多酚（儿茶素）已在各种实验系统中被证明具有抗肿瘤特性。一些报告表明 p53 肿瘤抑制蛋白参与其中，但其他报告则不然。因此，绿茶诱导抗肿瘤作用的确切分子机制尚不清楚。一种有前景的机制是儿茶素诱导细胞凋亡。事实上，已知儿茶素与细胞凋亡的诱导有关。在这方面，我们对这一新提案的假设是，包括儿茶素（-）表没食子儿茶素3-没食子酸酯（EGCG）、表儿茶素没食子酸酯（ECG）、表没食子儿茶素（EGC）和表儿茶素（EC）在内的绿茶成分的癌症化学预防作用是通过诱导细胞凋亡机制，包括诱导新鉴定的 TGF-β 超家族蛋白 NAG-1（非甾体抗炎药激活基因）。该假设的基本原理基于以下内容：1) NAG-1 基因被鉴定为饮食诱导基因，2) 正常结肠上皮细胞中的 NAG-1 表达高于邻近肿瘤细胞，3) NAG-1 具有亲我们和其他小组报告的细胞凋亡和抗肿瘤活性。因此，该项目的总体目标是鉴定单一儿茶素或儿茶素组合，以在人结直肠癌细胞中产生更高的 NGA-1 诱导剂。为了研究绿茶成分或其组合诱导 NAG-1 表达的分子机制，我们将使用两种不同的模型：HCT-116 人结直肠腺癌细胞和小鼠模型系统，其具体目标如下： 1. 定义转录调控机制负责通过 ECG 和其他儿茶素诱导 NAG-1。 2. ECG 治疗后基因表达的变化。 3.比较单独和组合儿茶素在结直肠癌动物模型中的预防和治疗效果。