Acylation as an Approach to Enhance the Cancer Preventive Effect of EGCG

酰化作为增强 EGCG 防癌效果的方法

• 批准号: 7637108
• 负责人: Shengmin Sang
• 金额: $ 6.75万
• 依托单位: NORTH CAROLINA CENTRAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-21 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7637108
• 关键词: Aberrant crypt foci; Acylation; Anhydrides; Animal Model; Azoxymethane; Bioavailable; Biological Availability; Blood; Cancerous; Cell Culture System; Cell Death Induction; Cell Line; Cells; Colon; Dicyclohexylcarbodiimide; Docosahexaenoic Acids; Dose; End Point; Epigallocatechin Gallate; Feces; Genus Cola; Growth; HT29 Cells; High Pressure Liquid Chromatography; Human; Induction of Apoptosis; Intestines; Malignant Neoplasms; Methods; Mus; Prevention; Preventive; Reaction; Tissues; acetic anhydride; base; behenic acid; carcinogenesis; cell growth; colon cancer cell line; gallocatechol; iodonitrotetrazolium; mouse model; pyridine; tumor growth; uptake

DESCRIPTION (provided by applicant): The objective of this project is to develop acylation as an approach to increase the stability, bioavailability, and cancer preventive activity of (-)-Epigallocatechin-3-gallate (EGCG), the major polyphenol from green tea. Previous studies have demonstrated that EGCG inhibited carcinogenesis and tumor growth in different animal models. However, EGCG is not very stable and has limited bioavailability. The rationale of this project is based on our recent results that peracetylated EGCG has greater cellular uptake and growth inhibitory activity in cell culture systems and higher bioavailability in mice as compared to EGCG. In this project, we will synthesize short-chain and long-chain acylated EGCG derivatives and compare the stability, cellular uptake, cell growth inhibition, and induction of apoptosis of these derivatives with those of EGCG. The two most bioavailable and bioactive derivatives will be synthesized in large quantities to study its inhibitory effect against aberrant crypt foci (ACF) formation in the azoxymethane (AOM)-treated mouse model. The inhibitory action will be correlated with the levels of EGCG in colon tissues and blood. We plan to accomplish our objective in the following specific aims: 1. To synthesize acylated derivatives of EGCG and to compare their stability, cellular uptake, cell growth inhibition, and induction of apoptosis in human colon cancer cell lines (HCT-116 and HT-29) with those of EGCG. 2. To determine the bioavailability and efficacy of acylated EGCG in the prevention of ACF formation in the AOM-treated mouse model.

描述（由申请人提供）： 该项目的目标是开发酰化方法，以提高 (-)-表没食子儿茶素-3-没食子酸酯 (EGCG)（绿茶中的主要多酚）的稳定性、生物利用度和癌症预防活性。先前的研究表明，EGCG 在不同的动物模型中抑制癌变和肿瘤生长。然而，EGCG 不太稳定，生物利用度有限。该项目的基本原理是基于我们最近的结果，即与 EGCG 相比，全乙酰化 EGCG 在细胞培养系统中具有更高的细胞摄取和生长抑制活性，并且在小鼠中具有更高的生物利用度。在本项目中，我们将合成短链和长链酰化EGCG衍生物，并将这些衍生物与EGCG的稳定性、细胞摄取、细胞生长抑制和诱导细胞凋亡等方面进行比较。将大量合成两种最具生物利用度和生物活性的衍生物，以研究其对氧化偶氮甲烷（AOM）处理的小鼠模型中异常隐窝病灶（ACF）形成的抑制作用。抑制作用与结肠组织和血液中 EGCG 的水平相关。我们计划通过以下具体目标来实现我们的目标： 1. 合成 EGCG 酰化衍生物，并比较它们在人结肠癌细胞系（HCT-116 和 HT-116）中的稳定性、细胞摄取、细胞生长抑制和凋亡诱导。 29）与EGCG的那些。 2. 确定酰化 EGCG 在 AOM 处理的小鼠模型中预防 ACF 形成的生物利用度和功效。