A new discovery by researchers at the Rensselaer Polytechnic Institute could pave the way for natural anti-cancer fighting using a protein called p53.
The findings, published in Nature Communications, shows that an anti-oxidant molecule found in green tea called epigallocatechin gallate (EGCG) directly interacts and increases levels of p53, an important protein that is often dysfunctional in cancer.
“Both p53 and EGCG molecules are extremely interesting. Mutations in p53 are found in over 50% of human cancer, while EGCG is the major antioxidant in green tea, a popular beverage worldwide,” said Professor Chunyu Wang, the corresponding author of the study, in a statement. “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.”
The p53 protein has important anti-cancer properties and because of the proteins' very flexible shape on its N-terminal end, it can perform various different functions in cells. It facilitates DNA repair and initiates cell death when DNA can't be repaired, a process called apoptosis. It also halts cell growth when things go wrong, all functions that go astray in cancer due to mutations or changes in p53 activity in cells.
P53 is normally present at low levels in cells. This is due to a natural cycle of production and degradation of the protein. When the N-terminal of the protein interacts with a molecule called MDM2, p53 is rapidly broken down. This leads to relatively low levels of p53 in cells but enough to perform its functions under normal conditions. However, in cancer, a lot of these functions go into overdrive, and if more p53 were available at this period, more could be done to combat cancer at a molecular level.
Now the new findings have shown that EGCG molecules present in abundance in green tea can prevent the degradation of p53 by interacting with the N-terminal end of the protein.
“Both EGCG and MDM2 bind at the same place on p53, the N-terminal domain, so EGCG competes with MDM2,” said Wang. “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 findings shape an important understanding of the molecular interactions of p53 and antioxidants and how the N-terminal of the protein might be used as a therapeutic target in the fight against cancer.
“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,” Curt Breneman, dean of the Rensselaer School of Science concluded.