Green tea compound helps p53, ‘guardian of the genome’ and tumor suppressor

An antioxidant found in green tea can increase levels of p53, a natural anti-cancer protein, known as the “guardian of the genome” for its ability to repair DNA damage or destroy cancer cells. Published today in Nature Communications, a study of the direct interaction between p53 and the green tea compound, epigallocatechin gallate (EGCG), points to a new target for cancer drug discovery.

“The p53 and EGCG molecules are extremely interesting. Mutations in p53 are found in more than 50% of human cancer, while EGCG is the main antioxidant in green tea, a popular drink worldwide,” said Chunyu Wang, corresponding author and professor of biological sciences at the Rensselaer Polytechnic Institute. “Now we find that there is a direct interaction hitherto unknown between the two, which points to a new path for the development of anticancer drugs. Our work helps to explain how EGCG is able to increase the anti-cancer activity of p53, opening the door to the development of drugs with EGCG-like compounds. “

Wang, a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies, specializes in using nuclear magnetic resonance spectroscopy to study specific mechanisms in Alzheimer’s disease and cancer, including p53, which he described as “arguably the most important protein in cancer. human “

P53 has several well-known anti-cancer functions, including stopping cell growth to allow DNA repair, activating DNA repair and initiating programmed cell death – called apoptosis – if DNA damage cannot be repaired. One end of the protein, known as the N-terminal domain, is flexible in shape and therefore can potentially serve several functions, depending on its interaction with various molecules.

EGCG is a natural antioxidant, which means that it helps to undo the almost constant damage caused by the use of oxygen metabolism. Found in abundance in green tea, EGCG is also packaged as an herbal supplement.

Wang’s team found that the interaction between EGCG and p53 preserves the protein from degradation. Normally, after being produced in the body, p53 is rapidly degraded when the N-terminal domain interacts with a protein called MDM2. This regular cycle of production and degradation keeps p53 levels at a constant low.

“Both EGCG and MDM2 bind at the same place in p53, the N-terminal domain, so EGCG competes with MDM2,” said Wang. “When EGCG binds to p53, the protein is not being degraded via MDM2, so the level of p53 will increase with direct interaction with EGCG, and that means there is more p53 for anticancer function. This is a very important interaction . “

“EGCG Binds Intrinsically Disordered N-Terminal Domain of p53 and Disrupts p53-MDM2 Interaction” was published with the support of several grants from the National Institutes of Health. In Rensselaer, Wang was accompanied in the research by Lauren Gandy, Weihua Jin, Lufeng Yan, Xinyue Liu and Yuanyuan Xiao. The first author, Jing Zhao, is a former member of Wang’s laboratory and is currently on the faculty of China Agricultural University in Beijing, China. Co-first author Alan Blaney is an MD-Ph.D. student at Upstate Medical University. The researchers also contributed to the SUNY Upstate Medical Center; the University of Massachusetts, Amherst; New York University; New York State University at Binghamton; NYU Shanghai; and Merck Research Laboratories.