Abstract
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.
Highlights
Many epidemiologic and laboratory studies have demonstrated accumulating evidence that a diet which has a high content of fruits and vegetables reduces the risk for several types of cancer [1, 2]
In this paper we review evidence indicating that EGCG exerts anticancer effects, at least in part, through inhibition of activation of the specific receptor tyrosine kinases (RTKs) and conclude that targeting RTKs and related signaling pathway by tea catechins might be a promising strategy for the prevention of human cancers
The cellular and molecular mechanisms by which specific phytochemicals cause such an anti-carcinogenic effect remain to be clarified, including the antioxidant activity and/or trapping of oxygen radicals, the induction of drug metabolizing and detoxifying enzymes, the promotion of DNA repair, and controlling the expression and functional activity of tumor-suppressor genes, etc [2,3,4]. In addition to these mechanisms, recent studies have demonstrated that phytochemicals exert an anti-carcinogenic effect by modulating the activities of various types of receptor tyrosine kinases (RTKs) and their downstream specific cell signaling pathways which are associated with the expression of the genes involved in cell proliferation and apoptosis [2, 5,6,7,8]
Summary
Many epidemiologic and laboratory studies have demonstrated accumulating evidence that a diet which has a high content of fruits and vegetables reduces the risk for several types of cancer [1, 2]. The cellular and molecular mechanisms by which specific phytochemicals cause such an anti-carcinogenic effect remain to be clarified, including the antioxidant activity and/or trapping of oxygen radicals, the induction of drug metabolizing and detoxifying enzymes, the promotion of DNA repair, and controlling the expression and functional activity of tumor-suppressor genes, etc [2,3,4] In addition to these mechanisms, recent studies have demonstrated that phytochemicals exert an anti-carcinogenic effect by modulating the activities of various types of receptor tyrosine kinases (RTKs) and their downstream specific cell signaling pathways which are associated with the expression of the genes involved in cell proliferation and apoptosis [2, 5,6,7,8]. The targeting of these signaling pathways may provide an effective strategy for the prevention and treatment of cancer because during the process of carcinogenesis, abnormalities in these pathways and/or the related downstream transcription factors are known to cause uncontrolled cell replication and malignant cell transformation [23,24]
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