Cardiothoracic Surgery, The Third XiangYa Hospital, Central South University, Changsha, Hunan 410013, PR China.
Oncol Rep. 2013 May;29(5):1983-90. doi: 10.3892/or.2013.2343. Epub 2013 Mar 12.
Epigallocatechin gallate (EGCG), which is derived from green tea, is well known for its chemopreventive activity. Several studies have shown that p53 plays an important role in the activity of EGCG; however, the mechanism by which EGCG regulates p53 requires further investigation. In the present study, we showed that EGCG inhibits anchorage-independent growth of human lung cancer cells by upregulating p53 expression. EGCG treatment can substantially increase p53 stability, promote nuclear localization of p53 and decrease nuclear accumulation of MDM2. We also found that EGCG increases the phosphorylation of p53 at Ser15 and Ser20 and enhances its transcriptional activity. Although EGCG promotes MDM2 expression in a p53-dependent manner, the interaction between MDM2 and p53 was significantly inhibited following EGCG treatment, which resulted in the inhibition of MDM2-mediated p53 ubiquitination. Thus, our results suggest that the stabilization and activation of p53 may partly contribute to the anticancer activity of EGCG.
没食子酸表没食子儿茶素酯（EGCG）源自绿茶，以其化学预防活性而闻名。多项研究表明，p53 在 EGCG 的活性中发挥重要作用；然而，EGCG 调节 p53 的机制需要进一步研究。在本研究中，我们表明 EGCG 通过上调 p53 表达来抑制人肺癌细胞的非锚定依赖性生长。EGCG 处理可显著增加 p53 的稳定性，促进 p53 的核定位并减少 MDM2 的核积累。我们还发现，EGCG 增加了 p53 在 Ser15 和 Ser20 位点的磷酸化，并增强了其转录活性。尽管 EGCG 以 p53 依赖性方式促进 MDM2 的表达，但 EGCG 处理后 MDM2 与 p53 之间的相互作用明显受到抑制，从而抑制了 MDM2 介导的 p53 泛素化。因此，我们的结果表明 p53 的稳定和激活可能部分有助于 EGCG 的抗癌活性。
