Antioxidant in green tea may lead to new anti-cancer drugs

Green tea contains an antioxidant that may boost the concentrations of p53—a natural anti-cancer protein, called the “guardian of the genome,” for its potential to kill cancerous cells or repair DNA damage.

Antioxidant in green tea may lead to new anti-cancer drugs
A compound found in green tea stabilizes an anti-cancer protein known as the “guardian of the genome.” Image Credit: Rensselaer Polytechnic Institute.

Recently published in the Nature Communications journal, a study of the direct interaction between the green tea compound, called epigallocatechin gallate (EGCG), and p53 underscores a new target for discovering new cancer drugs.

Both p53 and EGCG molecules are extremely interesting. 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.”

Chunyu Wang, Study Corresponding Author and Professor of Biological Sciences, Rensselaer Polytechnic Institute

Professor Wang continued, “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, who is also a member of the Rensselaer Center for Biotechnology and Interdisciplinary Studies, is a professional when it comes to using nuclear magnetic resonance spectroscopy for the analysis of specific mechanisms in cancer and Alzheimer’s disease, including p53, which according to him, is “arguably the most important protein in human cancer.”

P53 has many familiar anti-cancer functions, such as blocking the growth of cells to enable DNA repair, stimulating DNA repair, and triggering programmed cell death—known as apoptosis—if DNA damage cannot be reversed.

One end of the protein, called the N-terminal domain, has a flexible shape, and hence, can possibly serve many functions based on its interaction with numerous molecules.

EGCG is known to be a natural antioxidant, which means it helps to reverse the near constant damage induced by utilizing oxygen metabolism. EGCG is abundantly present in green tea and is also packaged as an herbal supplement.

Wang’s research team observed that the interaction between p53 and EGCG prevents the degradation of the protein. Usually, after being created inside the body, p53 is rapidly degraded when an interaction occurs between the N-terminal domain and a protein, known as MDM2. This routine cycle of production and degradation maintains the p53 concentrations at a low constant.

Both EGCG and MDM2 bind at the same place on p53, the N-terminal domain, so EGCG competes with MDM2. 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.”

Chunyu Wang, Study Corresponding Author and Professor of Biological Sciences, Rensselaer Polytechnic Institute

According to Curt Breneman, Dean of the Rensselaer School of Science, “By developing an understanding of the molecular-level mechanisms that control key biochemical interactions linked to devastating illnesses such as cancer and Alzheimer's disease, Chunyu's research is laying the groundwork for new and successful therapies.”

The study titled, “EGCG Binds Intrinsically Disordered N-Terminal Domain of p53 and Disrupts p53-MDM2 Interaction” was published with support from numerous grants from the National Institutes of Health.

Source:
Journal reference:

Zhao, J., et al. (2021) EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction. Nature Communications. doi.org/10.1038/s41467-021-21258-5.

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