Dong Z, Ma W, Huang C, Yang C S
The Hormel Institute, University of Minnesota, Austin 55912, USA.
Cancer Res. 1997 Oct 1;57(19):4414-9.
(-)-Epigallocatechin gallate (EGCG) and theaflavins are believed to be key active components in tea for the chemoprevention against cancer. However, the molecular mechanisms by which EGCG and theaflavins block carcinogenesis are not clear. We have used the JB6 mouse epidermal cell line, a system that has been used extensively as an in vitro model for tumor promotion studies, to examine the anti-tumor promotion effects of EGCG and theaflavins at the molecular level. EGCG and theaflavins inhibited epidermal growth factor- or 12-O-tetradecanoylphorbol-13-acetate-induced cell transformation in a dose-dependent manner. At the dose range (5-20 microM) that inhibited cell transformation, EGCG and theaflavins also inhibited AP-1-dependent transcriptional activity and DNA binding activity. The inhibition of AP-1 activation occurs through the inhibition of a c-Jun NH2-terminal kinase-dependent, but not an extracellular signal-regulated protein kinase (Erk) 1-dependent or Erk2-dependent, pathway. Because the transcription factor AP-1 is important for tumor promoter-induced neoplastic transformation, the inhibitory effects on AP-1 activation by EGCG and theaflavins may further explain the anti-tumor promotion action of these tea constituents.
（-）-表没食子儿茶素没食子酸酯（EGCG）和茶黄素被认为是茶叶中化学预防癌症的关键活性成分。然而，EGCG和茶黄素阻断致癌作用的分子机制尚不清楚。我们使用了JB6小鼠表皮细胞系，该系统已被广泛用作肿瘤促进研究的体外模型，以在分子水平上研究EGCG和茶黄素的抗肿瘤促进作用。EGCG和茶黄素以剂量依赖性方式抑制表皮生长因子或12-O-十四酰佛波醇-13-乙酸酯诱导的细胞转化。在抑制细胞转化的剂量范围（5-20 microM）内，EGCG和茶黄素还抑制AP-1依赖性转录活性和DNA结合活性。AP-1激活的抑制是通过抑制c-Jun NH2末端激酶依赖性途径，而不是细胞外信号调节蛋白激酶（Erk）1依赖性或Erk2依赖性途径实现的。由于转录因子AP-1对肿瘤启动子诱导的肿瘤转化很重要，因此EGCG和茶黄素对AP-1激活的抑制作用可能进一步解释了这些茶叶成分的抗肿瘤促进作用。
