Breast Cancer Prevention by Analogs of EGCG from Green Tea
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Breast cancer chemoprevention is gaining increasing acceptance as an effective method of cancer control, particularly in high risk patients. The recent approval of tamoxifen to reduce risk of breast cancer in high-risk women validates the ‘proof of principle’ that breast cancer chemoprevention is a achievable with appropriate small-molecule drugs. However, the risk/benefit ratio of tamoxifen still remains unclear because of tamoxifen’s association with the development of resistant tumors and side effects. Thus there remains a great need to develop new, and safer chemopreventive drugs and modalities. 
 
 
 
 
 
 
 
 The goal of the proposed research is to design and develop a preclinical chemopreventive drug candidate based on the natural product catechin, epigallocatechin-3-gallate (EGCG), found in green tea. This work builds on the promising results we obtained in our previous BCRP grant on the development of analogs of tea polyphenols for chemoprevention. Our successful development of the first versatile chemical synthesis of EGCG (and other catechins in green tea) allows us to modify the various portions of the EGCG molecule. We synthesized several analogs using our approach and one was found to be nearly as potent as EGCG itself in cell culture growth inhibition assays in both estrogen-dependent and ­independent breast cancer cell lines. 
 
 
 
 
 
 
 
 We now propose to build on our findings to discover novel preclinical drug candidates based on EGCG that will address the problems associated with the use of green tea and EGCG itself as chemopreventives. This research has high translational potential and addresses the BCRP Prevention and Innovative Treatment Modalities priority issues. 
 
 
 
 
 
 
 
 Green tea consumption is associated with decreased risk of breast, pancreatic, colon, esophageal, and lung cancers in humans. Green tea and EGCG are currently undergoing Phase I clinical trials and toxicology studies. However, a major problem with the use of green tea and EGCG as chemopreventives is the extremely low absorption of EGCG (
 
 
 
 
 
 Based on what is currently known about the chemopreventive action of EGCG, we propose to modify parts of the EGCG molecule that are not important for its chemopreventive activity in order to improve the oral absorption while maintaining chemopreventive activity. We will use synthesize EGCG analogs and test them. Our multidisciplinary approach enables us to study the absorption properties and metabolism of our analogs in in vitro laboratory assays for immediate feedback on our drug design and the validity of our approach. We thus avoid expensive animal testing and have a rapid, efficient way of finding the best chemopreventive candidates for more extensive preclinical testing. Since our drug design effort is based on a natural product with a long history of human use, it is likely that our analogs will be safe, an important attribute for chemopreventive agents designed for long term use. Safe, effective drugs for chemoprevention of breast cancer will contribute greatly to the physical and mental well-being of those at high risk for breast cancer.