Anti-cancer effects by the green tea catechins

绿茶儿茶素的抗癌作用

基本信息

批准号：
7050219
负责人：
SEUNG Joon BAEK
金额：
$ 21.28万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-04-06 至 2008-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7050219
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

项目摘要

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）：有说服力的流行病学证据，表明食用饮食多酚植物衍生的化合物减少了慢性疾病，例如癌症。包括美国在内的许多实验室研究表明，饮食化合物在体内和体外饮食中针对癌变的饮食化合物的抑制作用。绿茶及其组成的多酚（儿茶素）已被证明在多种实验系统中具有抗肿瘤特性。一些报告表明p53肿瘤抑制蛋白涉及，但其他报告则没有。因此，绿茶诱导抗肿瘤效应的确切分子机制尚不清楚。一种有希望的机制是儿茶素诱导凋亡。实际上，众所周知，儿茶素与凋亡的诱导有关。在这方面，我们对这一新建议的假设是，绿茶成分在内的癌症化学预防效应，包括儿茶素（ - ）上环蛋白酶3-甘油酸酯（EGCG）（EGCG），Epicatechin Gallate（ECG），Epigallocatechin（EGC）（EGC）和ECATECATECHIN（EC）的鉴定机制是一种新的鉴定机制TGF-β超家族蛋白NAG-1（非甾体类抗炎药激活的基因）。该假设的基本原理基于以下基础：1）鉴定Nag-1基因是饮食诱导的基因，2）正常结肠上皮中的Nag-1表达高于相邻的肿瘤细胞，3）NAG-NAG-1具有促凋亡性和抗肿瘤性和抗肿瘤性活性。因此，该项目的总体目标是鉴定人类结直肠癌细胞中较高NGA-1诱导剂的儿茶素的单个儿茶素或结合。为了研究绿茶成分或它们的组合诱导NAG-1表达的分子机制，我们将使用两个不同模型HCT-116 HUST-116人类大肠腺癌细胞和小鼠模型系统，具有以下特定目的：1。定义转录调节机制，负责ECG和其他Catechins诱导NAG-NAG-NAG-1。 2。ECG处理后基因表达的特征变化。 3。比较个体和结合儿茶素在结直肠癌模型中的预防和治疗功效。