Epigallocatechin-3-gallate (EGCG), a polyphenol found in the leaves of green tea (Camellia sinensis), can increase levels of the natural anti-cancer protein p53, often called ‘the guardian of the genome’, according to a new study led by scientists from the Rensselaer Polytechnic Institute.
Zhao et al. provide insights into the mechanisms of EGCG’s cancer activity and identify p53 N-terminal domain as a target for the discovery of cancer drugs through dynamic small molecule interactions. Image Credit: Sci-News.com.
Green tea, a popular beverage consumed worldwide, has been reported to have inhibitory effects on various types of cancer, such as breast cancer, lung, prostate and colon cancers.
Most chemo-preventing effects of green tea on cancer are attributed to polyphenol compounds, of which EGCG is the most important.
EGCG is responsible for 50-80% of the catechin in green tea. There is 200-300 mg of EGCG in a brewed cup (240 ml) of green tea.
P53 has several known cancer functions, including stopping cell growth to enable DNA repair, activating DNA repair, and initiating apoptosis if DNA damage cannot be repaired.
The one point of the protein, known as the N-terminal domain, has a flexible form and may therefore serve different functions depending on the interaction with multiple molecules.
“Both p53 and EGCG molecules are extremely interesting,” said Professor Chunyu Wang, a professor at the Polytechnic Institute of Rensselaer.
“Mutations in p53 occur in more than 50% of human cancers, while EGCG is the major antioxidant in green tea, a popular beverage worldwide.”
“Now we find that there is a previously unknown, direct interaction between the two, which points to a new path for the development of anticancer drugs.”
“Our work helps explain how EGCG can promote the anti-cancer activity of p53, which opens the door to the development of drugs with EGCG-like compounds.”
Professor Wang and colleagues found that the interaction between EGCG and p53 preserves the protein of degradation.
After production in the body, p53 is usually rapidly degraded when the N-terminal domain interacts with a protein called MDM2.
This regular cycle of production and deterioration keeps p53 levels at a low constant.
“Both EGCG and MDM2 bind in the same place on p53, the N-terminal domain, so that EGCG competes with MDM2,” Professor Wang said.
“When EGCG binds with p53, the protein is not broken down by MDM2, so the level of p53 will increase with the direct interaction with EGCG, which means that there is more p53 for the action of cancer. This is a very important interaction. ”
The study was published in the journal Nature communication.
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J. Zhao et al. 2021. EGCG binds intrinsically disrupted N-terminal domain of p53 and disrupts p53-MDM2 interaction. Nat Commun 12, 986; doi: 10.1038 / s41467-021-21258-5