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.