Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases

Abstract

Recent studies indicate that receptor tyrosine kinases (RTKs), which play important roles in cell proliferation, are one of the possible targets of green tea catechins (GTCs) in cancer cell growth inhibition. (-)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, inhibits cell proliferation and induces apoptosis in various types of cancer cells, including colorectal cancer and hepatocellular carcinoma cells, by blocking the activation of the epidermal growth factor receptor (EGFR) family of RTKs. EGCG inhibits the activation of insulin-like growth factor-1 receptor (IGF-1R) and VEGFR2, the other members of the RTK family, and this effect is also associated with the anticancer and chemopreventive properties of this agent. EGCG suppresses the activation of EGFR in part by altering membrane lipid organization and causing the subsequent inhibition of the dimerization and activation of this receptor. Preliminary trials have shown that GTCs successfully prevent the development and progression of precancerous lesions, such as colorectal adenomas, without causing severe adverse effects. The present report reviews evidence indicating that GTCs exert anticancer and chemopreventive effects by inhibiting the activation of specific RTKs, especially EGFR, IGF-1R, and VEGFR2, and concludes that targeting RTKs and their related signaling pathways by using tea catechins could be a promising strategy for the prevention of human cancers.

Green Tea Catechins for Prostate Cancer Prevention: Present Achievements and Future Challenges

“…GTCs interferes directly or indirectly with the formation of the ligand-receptor complex of several cell surface receptors [55,56]. Three different mechanisms have been proposed to explain the effect of GTCs on the regulation of the activity of cell surface receptors and their signaling pathways.…”

“…The second mechanism involves the suppression of the intrinsic activity of lipid rafts-associated signaling proteins by lipid rafts disruption [55,61,62]. The third prevents the interaction between receptor and ligand promoting receptor clearance through physical sequestration inside endosomal vesicles [63].…”

“…Receptor tyrosine kinases (RTKs) have been recently identified as targets of GTCs in cancer cell growth inhibition [55,64,65]. The binding of a growth factor or a cytokine to the extracellular domain of RTKs induces the dimerization and autophosphorylation of the RTKs on specific tyrosine residues and activation of downstream intracellular signaling that include Ras/ERK/MAPK and PI3K/Akt.…”

“…The activation of cell surface RTKs controls many key important processes in normal cells such as cell proliferation, differentiation, survival and migration. These receptor-associated pathways have been found altered in tumors cells, including PCa [55,[66][67][68][69]. The RTKs family comprises epidermal growth factor receptors (EGFRs), fibroblast growth factor receptors (FGFRs), insulin-like growth factor receptors (IGF-R), platelet-derived growth factor receptors (PDGFRs), vascular endothelial growth factor receptors (VEGFRs), hepatocyte growth factor receptors (HGFRs) also known as Met.…”

Amplification by (-)-epigallocatechin gallate and chlorogenic acid of TNF-α-stimulated interleukin-6 synthesis in osteoblasts

“…Green tea has been consumed mainly in Eastern countries, while coffee is consumed throughout the world. (-)-Epigallocatechin gallate (EGCG), the most abundant catechin and a major bioactive component in green tea, and chlorogenic acid (CGA), a main phenolic compound in coffee, have beneficial properties for human health, such as antioxidation, anti-inflammation and cancer prevention (1)(2)(3).…”