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）： 该项目的目的是开发酰基化作为提高（ - ） - epigallocatechin-3-gallate（EGCG）的稳定性，生物利用度和癌症预防活性的方法，这是绿茶中的主要多酚。先前的研究表明，EGCG在不同动物模型中抑制了癌变和肿瘤的生长。但是，EGCG不是很稳定，并且生物利用度有限。该项目的基本原理是基于我们最近的结果，即与EGCG相比，在细胞培养系统中，过乙酰化的EGCG在细胞培养系统中具有更大的细胞摄取和生长抑制活性，而小鼠的生物利用度更高。在这个项目中，我们将合成短链和长链酰化EGCG衍生物，并比较这些衍生物的稳定性，细胞摄取，细胞生长抑制以及诱导这些衍生物的凋亡与EGCG的凋亡。将大量生物可生物利用和生物活性衍生物大量合成，以研究其对甲氧基甲烷（AOM）处理的小鼠模型中异常隐窝灶（ACF）形成的抑制作用。抑制作用将与结肠组织和血液中的EGCG水平相关。我们计划在以下特定目的中实现目标：1。合成EGCG的酰化衍生物，并比较其稳定性，细胞摄取，细胞生长抑制以及人类结肠癌细胞系中凋亡（HCT-116和HT-29）中凋亡的诱导与EGCG的凋亡。 2。确定酰化EGCG在预防ACF形成中的生物利用度和功效。