This is a new R01 application to investigate the molecular targets of the chemopreventive effect on cancer by tea polyphenols. Recently, we have identified a few polyphenol (-)epigallocatechin 3-gallate (EGCG) binding proteins. Because these EGCG-binding proteins are critical for cell growth, neoplastic cell transformation and tumorigenicity, we hypothesize that the chemopreventive effect of the tea polyphenol EGCG and its derivatives is derived from their target on these proteins. We will use 3H-EGCG cell culture and protein analysis to examine the anti-tumor promotion activity of tea polyphenols.
The specific aims to addrress the hypothesis are 1) to study the role of newly identified EGCG-binding proteins in tumor promoter-induced cell growth and cell transformation; 2) to study the role of EGCG-binding proteins in chemopreventive activity of EGCG and other tea polyphenols by using cell culture models; 3) to study the interactions of EGCG with its binding protein fyn and IGF-1R; 4) to study the role of fyn and IGF-1R as molecular targets for the anti-tumor effect of EGCG in vivo in tumor xenograft model. We have established experimental conditions through preliminary investigations and expect that the proposed molecular mechanism studies will lead to the development of better chemopreventive agents and facilitate the design of more effective chemoprevention trials. ? ? ?
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