Epigallocatechin-3-gallate (EGCG), a polyphenol found in green tea leaves (Camellia sinensis), may increase the level of the natural protein against cancer p53, often called the “genome keeper”, according to a new study conducted by scientists at the Rensselaer Polytechnic Institute.
Green tea, a popular beverage consumed around the world, is reported to have inhibitory effects against various types of cancer, such as breast, lung, prostate and colon cancers.
Most of the chemo-preventive effects of green tea on cancer are attributed to polyphenol compounds, among which EGCG is the most important.
EGCG makes up 50-80% of the catechins in green tea. The brewed cup (240 ml) of green tea contains 200-300 mg of EGCG.
P53 has several well-known anticancer functions, including arresting cell growth to allow DNA repair, activating DNA repair, and initiating apoptosis if DNA damage cannot be repaired.
One end of the protein, known as the N-terminal domain, has a flexible shape and therefore can potentially serve several functions, depending on the interaction with multiple molecules.
“Both the p53 and EGCG molecules are extremely interesting,” said Runselaer Polytechnic Institute professor Chunyu Wang.
“Mutations in p53 are found in over 50% of human cancers, while EGCG is the main antioxidant in green tea, a popular beverage around the world.”
“We are now discovering that there is a previously unknown, direct interaction between the two, indicating a new path for the development of cancer drugs.”
“Our work helps explain how EGCG is able to enhance the anticancer activity of p53, opening the door to drug development with compounds similar to EGCG.”
Professor Wang and colleagues found that the interaction between EGCG and p53 keeps the protein from degrading.
Typically, upon formation in the body, p53 is rapidly degraded when the N-terminal domain interacts with a protein called MDM2.
This regular production and decomposition cycle maintains the p53 level at a low constant.
“Both EGCG and MDM2 bind at the same site on the p53, N-terminal domain, so EGCG competes with MDM2,” Professor Wang said.
“When EGCG binds to p53, the protein is not broken down through MDM2, so the p53 level will increase by direct interaction with EGCG, which means it has more p53 for anti-cancer function. This is a very important interaction. ”
The study was published in the journal Nature Communications.
J. Zhao and others. 2021. EGCG binds the substantially disordered N-terminal domain of p53 and disrupts the p53-MDM2 interaction. Nat Commun 12, 986; doi: 10.1038 / s41467-021-21258-5