Tea Research Institute Chinese Academy of Agricultural Sciences, Ministry of Agriculture, Hangzhou 310008, China.
Department of Tea Science, Zhejiang University, Hangzhou 310058, China.
Molecules. 2019 Feb 14;24(4):673. doi: 10.3390/molecules24040673.
Theaflavin-3,3'-digallate (TF3) is a unique polyphenol in black tea. Epidemiological studies have proved that black tea consumption decreases the incidence rate of ovarian cancer. Our former research demonstrated that TF3 inhibited human ovarian cancer cells. Nevertheless, the roles of checkpoint kinase 2 (Chk2) and p27 kip1 (p27) in TF3-mediated inhibition of human ovarian cancer cells have not yet been investigated. In the current study, TF3 enhanced the phosphorylation of Chk2 to modulate the ratio of pro/anti-apoptotic Bcl-2 family proteins to initiate intrinsic apoptosis in a p53-independent manner and increased the expression of death receptors to activate extrinsic apoptosis in OVCAR-3 human ovarian carcinoma cells. In addition, TF3 up-regulated the expression of p27 to induce G0/G1 cell cycle arrest in OVCAR-3 cells. Our study indicated that Chk2 and p27 were vital anticancer targets of TF3 and provided more evidence that TF3 might be a potent agent to be applied as adjuvant treatment for ovarian cancer.
茶黄素-3,3'-双没食子酸酯（TF3）是红茶中特有的多酚。流行病学研究已经证明，红茶的摄入可降低卵巢癌的发病率。我们之前的研究表明，TF3 可抑制人卵巢癌细胞。然而，TF3 介导的人卵巢癌细胞抑制作用中，细胞检验点激酶 2（Chk2）和 p27kip1（p27）的作用尚未被研究。在本研究中，TF3 通过增强 Chk2 的磷酸化，以非依赖 p53 的方式调节促凋亡/抗凋亡 Bcl-2 家族蛋白的比例，启动内在凋亡，并增加死亡受体的表达，激活 OVCAR-3 人卵巢癌细胞的外在凋亡。此外，TF3 上调了 p27 的表达，诱导 OVCAR-3 细胞发生 G0/G1 期细胞周期阻滞。本研究表明，Chk2 和 p27 是 TF3 的重要抗癌靶点，为 TF3 可能作为卵巢癌辅助治疗的有效药物提供了更多证据。
