Deguchi Hiroko, Fujii Teruhiko, Nakagawa Shino, Koga Toshihiro, Shirouzu Kazuo
Department of Surgery, Kurume University School of Medicine, Kurume 830-0011, Japan.
Int J Oncol. 2002 Dec;21(6):1301-5.
We have investigated the cell growth inhibitory effects of crude catechin (catechin) containing approximately 53% of epigallocatechin-3-gallate (EGCG) on the human breast cancer cell line T47D, and the mechanism of its action, with emphasis on the cell cycle and mitogen-activated protein kinases (MAPK). A significant dose-dependent growth inhibition was observed after treatment with catechin. At 48 h after the addition of catechin, cells at the G2/M phase were increased by 8.3%, compared with the control. Analysis of the expression of cell cycle-related proteins after the addition of catechin showed that the cyclin-dependent kinase (cdk) 2 and the cdk4 proteins were decreased after administration, the expression of cyclin A protein was increased at 24 h after administration, however, the expression of the cyclin D1 and cyclin E proteins was unchanged. At 24 h after the administration of catechin, the phosphorylation of cell division cycle 2 (cdc2) was inhibited, and the expression of cyclin B1 protein was also decreased. Furthermore, the analysis of the MAPK expression showed that the phosphorylated JNK/SAPK protein began to increase at 3 h after catechin administration, and the expression persisted until 24 h after administration, then decreased. The phosphorylation of p38 protein was increased at 12 h, and began to decrease at 36 h after catechin administration. Based on these results, we speculate that, in the breast cancer cell line T47D, catechin phosphorylated JNK/SAPK and p38, and that the phosphorylated JNK/SAPK and p38 inhibited the phosphorylation of cdc2, and regulated the expression of cyclin A, cyclin B1, and cdk proteins, thereby causing G2 arrest. The results suggested that catechin (EGCG) may be an effective adjuvant therapy after breast cancer surgery.
我们研究了含有约53%表没食子儿茶素-3-没食子酸酯（EGCG）的粗儿茶素（儿茶素）对人乳腺癌细胞系T47D的细胞生长抑制作用及其作用机制，重点关注细胞周期和丝裂原活化蛋白激酶（MAPK）。用儿茶素处理后观察到显著的剂量依赖性生长抑制。添加儿茶素后48小时，与对照组相比，处于G2/M期的细胞增加了8.3%。添加儿茶素后对细胞周期相关蛋白表达的分析表明，给药后细胞周期蛋白依赖性激酶（cdk）2和cdk4蛋白减少，给药后24小时细胞周期蛋白A蛋白表达增加，然而，细胞周期蛋白D1和细胞周期蛋白E蛋白的表达没有变化。给药儿茶素后24小时，细胞分裂周期2（cdc2）的磷酸化受到抑制，细胞周期蛋白B1蛋白的表达也降低。此外，对MAPK表达的分析表明，磷酸化的JNK/SAPK蛋白在儿茶素给药后3小时开始增加，并持续表达至给药后24小时，然后下降。p38蛋白的磷酸化在给药后12小时增加，并在给药后36小时开始下降。基于这些结果，我们推测，在乳腺癌细胞系T47D中，儿茶素使JNK/SAPK和p38磷酸化，并且磷酸化的JNK/SAPK和p38抑制cdc2的磷酸化，并调节细胞周期蛋白A、细胞周期蛋白B1和cdk蛋白的表达，从而导致G2期阻滞。结果表明，儿茶素（EGCG）可能是乳腺癌手术后一种有效的辅助治疗方法。
