Department of Metabolism and Nutrition, Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
Nutr Cancer. 2013;65(5):718-28. doi: 10.1080/01635581.2013.795981.
The tea flavonoid epicatechin gallate (ECG) exhibits a wide range of biological activities. In this study, the in vitro anticancer effects of ECG on SW480 colon cancer cell line was investigated by analyzing the cell cycle, apoptosis, key proteins involved in cellular survival/proliferation, namely AKT/phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinases (MAPKs), and the role of p53 in these processes. ECG induced cell cycle arrest at the G0/G1-S phase border associated with the stimulation of p21, p-p53, and p53 and the suppression of cyclins D1 and B1. Exposure of SW480 cells to ECG also led to apoptosis as determined by time-dependent changes in caspase-3 activity, MAPKs [extracellular regulated kinase (ERK), p38, and c-jun amino-terminal kinase (JNK)], p21 and p53 activation, and AKT inhibition. The presence of pifithrin, an inhibitor of p53 function, blocked ECG-induced apoptosis as was manifested by restored cell viability and caspase-3 activity to control values and reestablished the balance among Bcl-2 anti- and proapoptotic protein levels. Interestingly, ECG also inhibited p53 protein and RNA degradation, contributing to the stabilization of p53. In addition, JNK and p38 have been identified as necessary for ECG-induced apoptosis, upon activation by p53. The results suggest that the activation of the p53-p38/JNK cascade is required for ECG-induced cell death in SW480 cells.
表没食子儿茶素没食子酸酯（ECG）具有广泛的生物活性。本研究通过分析细胞周期、细胞凋亡、参与细胞存活/增殖的关键蛋白，即 AKT/磷脂酰肌醇-3-激酶（PI3K）和丝裂原激活蛋白激酶（MAPKs），以及 p53 在这些过程中的作用，研究了 ECG 对 SW480 结肠癌细胞系的体外抗癌作用。ECG 诱导细胞周期停滞在 G0/G1-S 期边界，伴随着 p21、p-p53 和 p53 的刺激以及细胞周期蛋白 D1 和 B1 的抑制。SW480 细胞暴露于 ECG 也会导致细胞凋亡，这可以通过 caspase-3 活性、MAPKs（细胞外调节激酶（ERK）、p38 和 c-jun 氨基末端激酶（JNK））、p21 和 p53 激活以及 AKT 抑制的时间依赖性变化来确定。p53 功能抑制剂 pifithrin 的存在阻断了 ECG 诱导的细胞凋亡，表现为细胞活力和 caspase-3 活性恢复到对照值，并重新建立了 Bcl-2 抗凋亡蛋白和促凋亡蛋白之间的平衡。有趣的是，ECG 还抑制了 p53 蛋白和 RNA 的降解，有助于 p53 的稳定。此外，JNK 和 p38 已被确定为 p53 激活后参与 ECG 诱导的细胞凋亡所必需的。结果表明，p53-p38/JNK 级联的激活是 ECG 诱导 SW480 细胞死亡所必需的。
