Yeh C-W, Chen W-J, Chiang C-T, Lin-Shiau S-Y, Lin J-K
Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Pharmacogenomics J. 2003;3(5):267-76. doi: 10.1038/sj.tpj.6500192.
Tea is a heavily consumed beverage world wide because of its unique aroma, less cost and broad availability. Fatty acid synthase (FAS) is a key enzyme in lipogenesis. FAS is overexpressed in the malignant human breast carcinoma MCF-7 cells and its expression is further enhanced by the epidermal growth factor (EGF). The EGF-induced expression of FAS was inhibited by green and black tea extracts. The expression of FAS was also suppressed by the tea polyphenol (-)-epigallocatechin 3-gallate (EGCG), theaflavin (TF-1), TF-2 and theaflavin 3,3'-digallate(TF-3) at both protein and mRNA levels that may lead to the inhibition of cell lipogenesis and proliferation. Both EGCG and TF-3 inhibit the activation of Akt and block the binding of Sp-1 to its target site. Furthermore, the EGF-induced biosyntheses of lipids and cell proliferation were significantly suppressed by EGCG and TF-3. These findings suggest that tea polyphenols suppress FAS expression by downregulating EGF receptor/PI3K/Akt/Sp-1 signal transduction pathway, and tea and tea polyphenols might induce hypolipidemic and antiproliferative effects by suppressing FAS.
由于其独特的香气、较低的成本和广泛的可得性，茶在全球范围内是一种消费量大的饮品。脂肪酸合酶（FAS）是脂肪生成中的关键酶。FAS在人恶性乳腺癌MCF-7细胞中过表达，并且其表达通过表皮生长因子（EGF）进一步增强。绿茶和红茶提取物抑制了EGF诱导的FAS表达。茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）、茶黄素（TF-1）、TF-2和茶黄素-3,3'-双没食子酸酯（TF-3）在蛋白质和mRNA水平上也抑制了FAS的表达，这可能导致细胞脂肪生成和增殖的抑制。EGCG和TF-3均抑制Akt的激活并阻断Sp-1与其靶位点的结合。此外，EGCG和TF-3显著抑制了EGF诱导的脂质生物合成和细胞增殖。这些发现表明，茶多酚通过下调EGF受体/PI3K/Akt/Sp-1信号转导途径来抑制FAS表达，并且茶和茶多酚可能通过抑制FAS诱导降血脂和抗增殖作用。
