Epigallocatechin-3-gallate (EGCG), a polyphenol found in the leaves of green tea (Camellia sinensis), may increase levels of the natural anti-cancer protein p53, often referred to as ‘the guardian of the genome,’ according to a new study led by Rensselaer Polytechnic Institute scientists.
Green tea, a popular beverage consumed worldwide, has been reported to have inhibitory effects against various types of cancer, such as breast, lung, prostate, and colon cancer.
Most of the chemo-preventive effects of green tea on cancer are attributed to polyphenol compounds, among which EGCG is the most important.
EGCG accounts 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 well-known anti-cancer functions, including halting cell growth to allow for 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 its interaction with multiple molecules.
“Both p53 and EGCG molecules are extremely interesting,” said Rensselaer Polytechnic Institute’s Professor Chunyu Wang.
“Mutations in p53 are found in over 50% of human cancer, while EGCG is the major anti-oxidant 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 developing anti-cancer drugs.”
“Our work helps to explain how EGCG is able to boost p53’s anti-cancer activity, opening the door to developing drugs with EGCG-like compounds.”
Professor Wang and colleagues found that the interaction between EGCG and p53 preserves the protein from degradation.
Typically, after being produced within the body, p53 is quickly degraded when the N-terminal domain interacts with a protein called MDM2.
This regular cycle of production and degradation holds p53 levels at a low constant.
“Both EGCG and MDM2 bind at the same place on p53, the N-terminal domain, so EGCG competes with MDM2,” Professor Wang said.
“When EGCG binds with p53, the protein is not being degraded through MDM2, so the level of p53 will increase with the direct interaction with EGCG, and that means there is more p53 for anti-cancer function. This is a very important interaction.”
The study was published in the journal Nature Communications.
J. Zhao et al. 2021. EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction. Nat Commun 12, 986; doi: 10.1038/s41467-021-21258-5
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