The major polyphenolic compound in green tea, epigallocatechin-3-gallate (EGCG), has been shown to induce apoptosis in cancer cells, but its molecular mechanism is not fully understood. Recently, a team led by Chunyu Wang at Rensselaer Polytechnic Institute (with China Agricultural University as the first affiliation and Jing Zhao as the first author of the paper) published a research paper in Nature Communications titled "EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction". Using SPR and NMR techniques, the study found that EGCG directly interacts with the tumor suppressor p53, with the intrinsically disordered N-terminal domain (NTD) identified as the main binding site. Large-scale atomic simulations, SAXS and AUC results showed that the EGCG-NTD interaction is dynamic, and EGCG leads to the appearance of a subset of compact bound conformations. The EGCG-p53 interaction disrupts the interaction between p53 and its regulatory E3 ligase MDM2, and inhibits MDM2-mediated ubiquitination of p53 in vitro, potentially stabilizing p53's anti-tumor activity. This study provides insights into the anti-cancer mechanism of EGCG and identifies the p53 NTD as a target for cancer drug discovery through its dynamic interaction with small molecules.
In recent years, diet-based cancer prevention and treatment have received considerable attention. Green tea is a popular beverage worldwide and has been reported to have inhibitory effects on various types of cancer, such as breast cancer, lung cancer, prostate cancer, and colon cancer. Epigallocatechin-3-gallate (EGCG) is one of the most important polyphenolic compounds in green tea, accounting for 50-80% of catechins. A cup of brewed green tea (240 mL) contains 200-300 mg of EGCG. By drinking a cup of green tea or taking EGCG tablets, a serum concentration of 0.1-1 μM EGCG can be achieved. The anti-cancer effect of EGCG has been confirmed in epidemiological, cell culture, animal studies, and clinical trials.
EGCG in green tea has been shown to promote growth arrest and induce apoptosis in various human cancer cell lines, including prostate cancer cells, epidermoid carcinoma cells, bladder cancer cells, and colon cancer cells. In mice, oral administration of green tea or intravenous injection of purified EGCG can inhibit angiogenesis and suppress solid tumor growth. At the molecular level, EGCG interacts with cancer-related proteins, such as glucose-regulated protein 78 (GRP78) and Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1).
p53 is an important tumor suppressor that promotes cell cycle arrest or apoptosis, and plays a crucial role in tumor therapy as a response to cellular stress stimuli. The interaction between EGCG and p53 may be a novel therapeutic strategy to enhance p53's anti-tumor activity.
EGCG is a natural product widely present in green tea, with various biological activities including antioxidant, anti-inflammatory, and anti-cancer properties. EGCG is considered one of the most active anti-cancer components in green tea. EGCG may exert its anti-cancer activity through multiple mechanisms, including regulating cell cycle, inducing apoptosis, and inhibiting angiogenesis.
EGCG has been extensively studied over the past few decades, but its anti-cancer mechanism is not fully understood. Recently, a study found that EGCG can directly interact with p53 and stabilize its anti-tumor activity. The study used surface plasmon resonance spectroscopy and nuclear magnetic resonance techniques to determine the direct interaction between EGCG and p53, and identified the intrinsically disordered N-terminal domain (NTD) as the main binding site for EGCG and p53.
The study also found that EGCG can disrupt the interaction between p53 and its regulatory E3 ligase MDM2, and inhibit MDM2-mediated ubiquitination of p53 in vitro, potentially stabilizing p53's anti-tumor activity. These results suggest that EGCG may exert its anti-cancer activity by directly interacting with p53.
In summary, EGCG is a natural product with various biological activities including antioxidant, anti-inflammatory, and anti-cancer properties. Recent studies have shown that EGCG can directly interact with p53 and stabilize its anti-tumor activity, providing a new mechanism for the application of EGCG in cancer therapy. These findings suggest that EGCG may be a promising anti-cancer compound worthy of further investigation.
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