Targeting receptor tyrosine kinases for chemoprevention by green tea catechin, EGCG.
Targeting receptor tyrosine kinases for chemoprevention by green tea catechin, EGCG.
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DOI：
10.3390/ijms9061034
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发表时间：
2008-06
影响因子：
5.6
通讯作者：
Moriwaki H
中科院分区：
文献类型：
--
作者：
Shimizu M;Shirakami Y;Moriwaki H
茶是世界上最受欢迎的饮料之一。流行病学研究表明，喝茶，特别是绿色茶，与癌症的发展呈反比关系。大量的体内和体外研究表明，绿色茶及其成分对各种器官的癌症具有很强的化学预防作用。（-）-表没食子儿茶素-3-没食子酸酯（EGCG），绿色茶中的主要儿茶素，似乎是茶中在抑制细胞增殖和诱导癌细胞凋亡方面最具生物活性的成分。最近的研究表明，受体酪氨酸激酶（RTK）是EGCG抑制肿瘤细胞生长的关键靶点之一。EGCG抑制EGFR（erbB 1）、HER 2（neu/erbB 2）以及HER 3（neu/erbB 3）在各种类型的人类癌细胞中的活化，这些细胞属于RTK超家族的亚类I。ERG还抑制RTK家族其他成员IGF-1和VEGF受体的激活。此外，EGCG改变膜脂质组织，从而抑制EGFR的二聚化和活化。因此，EGCG抑制Ras/MAPK和PI 3 K/Akt信号通路（其为RTK相关的细胞信号通路）以及AP-1和NF-κB的活化，从而调节与癌细胞中诱导凋亡和细胞周期停滞相关的靶基因的表达。这些发现是重要的，因为RTK及其下游效应物的表达和功能异常在几种类型的人类恶性肿瘤的发展中起着关键作用。在本文中，我们回顾证据表明，EGCG发挥抗癌作用，至少部分，通过抑制特定的RTK的激活，并得出结论，茶儿茶素靶向RTK和相关的信号通路可能是一个有前途的策略，为预防人类癌症。
Tea is one of the most popular beverages consumed worldwide. Epidemiologic studies show an inverse relationship between consumption of tea, especially green tea, and development of cancers. Numerous in vivo and in vitro studies indicate strong chemopreventive effects for green tea and its constituents against cancers of various organs. (–)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, appears to be the most biologically active constituent in tea with respect to inhibiting cell proliferation and inducing apoptosis in cancer cells. Recent studies indicate that the receptor tyrosine kinases (RTKs) are one of the critical targets of EGCG to inhibit cancer cell growth. EGCG inhibits the activation of EGFR (erbB1), HER2 (neu/erbB2) and also HER3 (neu/erbB3), which belong to subclass I of the RTK superfamily, in various types of human cancer cells. The activation of IGF-1 and VEGF receptors, the other members of RTK family, is also inhibited by EGCG. In addition, EGCG alters membrane lipid organization and thus inhibits the dimerization and activation of EGFR. Therefore, EGCG inhibits the Ras/MAPK and PI3K/Akt signaling pathways, which are RTK-related cell signaling pathways, as well as the activation of AP-1 and NF-κB, thereby modulating the expression of target genes which are associated with induction of apoptosis and cell cycle arrest in cancer cells. These findings are significant because abnormalities in the expression and function of RTKs and their downstream effectors play a critical role in the development of several types of human malignancies. In this paper we review evidence indicating that EGCG exerts anticancer effects, at least in part, through inhibition of activation of the specific RTKs and conclude that targeting RTKs and related signaling pathway by tea catechins might be a promising strategy for the prevention of human cancers.
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