Tea catechins as inhibitors of receptor tyrosine kinases: mechanistic insights and human relevance.
Receptor tyrosine kinases (RTKs) play important roles in the control of fundamental cellular processes, influencing the balance between cell proliferation and death. RTKs have emerged as molecular targets for the treatment of various cancers. Green tea and its polyphenolic compounds, the catechins, exhibit chemopreventive and chemotherapeutic properties in many human cancer cell types, as well as in various carcinogenicity models in vivo. Epidemiological studies are somewhat less convincing, but some positive correlations have been observed. The tea catechins, including (-)-epigallocatechin-3-gallate (EGCG), have pleiotropic effects on cellular proteins and signaling pathways. This review focuses on the ability of the tea constituents to suppress RTK signaling, and summarizes the mechanisms by which EGCG and other catechins might exert their protective effects towards dysregulated RTKs in cancer cells. The findings are discussed in the context of ongoing clinical trials with RTK inhibitors, and the possibility for drug/nutrient interactions enhancing therapeutic efficacy.
Larsen
Christine A
CA
Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
Dashwood
Roderick H
RH
Bisson
William H
WH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002392:Catechin / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013662:Tea / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D013662:Tea; D002392:Catechin; D020794:Receptor Protein-Tyrosine Kinases