© 2006 The Japanese Biochemical Society.
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Tannic Acid, a Potent Inhibitor of Epidermal Growth Factor Receptor Tyrosine Kinase
1 Hepatitis Viruses and Liver Cancer Research Laboratory, School of Chemical and Biomedical Engineering, Nanyang Technological University, 19 Nanyang Drive, Singapore 637551; 2 Department of Computational Science, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260; and 3 Department of Experimental Surgery, Singapore General Hospital, Outram Road, Singapore 169608
* To whom correspondence should be addressed. Tel: +65 63162870, E-mail: EBYang{at}ntu.edu.sg
Increasing evidence supports the hypothesis that tannic acid, a plant polyphenol, exerts anticarcinogenic activity in chemically induced cancers. In the present study, tannic acid was found to strongly inhibit tyrosine kinase activity of epidermal growth factor receptor (EGFr) in vitro (IC50 = 323 nM). In contrast, the inhibition by tannic acid of p60c-src tyrosine kinase (IC50 = 14 µM) and insulin receptor tyrosine kinase (IC50 = 5 µM) was much weaker. The inhibition of EGFr tyrosine kinase by tannic acid was competitive with respect to ATP and non-competitive with respect to peptide substrate. In cultured cells, growth factor–induced tyrosine phosphorylation of growth factor receptors, including EGFr, platelet-derived growth factor receptor, and basic fibroblast growth factor receptor, was inhibited by tannic acid. No inhibition of insulin-induced tyrosine phosphorylation of insulin receptor and insulin-receptor substrate-1 was observed. EGF-stimulated growth of HepG2 cells was inhibited in the presence of tannic acid. The inhibition of serine/threonine-specific protein kinases, including cAMP-dependent protein kinase, protein kinase C and mitogen-activated protein kinase, by tannic acid was only detected at relatively high concentration, IC50 being 3, 325 and 142 µM respectively. The molecular modeling study suggested that tannic acid could be docked into the ATP binding pockets of either EGFr or insulin receptor. These results demonstrate that tannic acid is an in vitro potent inhibitor of EGFr tyrosine kinase.
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