Inhibition of oncogene product enzyme activity as an approach to cancer chemoprevention. Tyrosine-specific protein kinase inhibition by purpurogallin from Quercus sp. Nutgall

✍ Scribed by Mohamed Abou-Karam; Dr. W. Thomas Shier

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 56 KB
• Volume: 13
• Category: Article
• ISSN: 0951-418X
• DOI: 10.1002/(sici)1099-1573(199906)13:4<337::aid-ptr451>3.0.co;2-j

✦ Synopsis

Inhibitors of oncogene product enzyme activity were sought as a prescreen for potential cancer chemopreventive agents. Purpurogallin, a polyphenol from Quercus sp. nutgall, was found to inhibit the tyrosine-specific protein kinase of the human erb-b oncogene product (epidermal growth factor receptor) for both autophosphorylation (IC 50 = 27.5 mM) and phosphorylation of an exogenous substrate (IC 50 = 45.3 mM). An examination of enzyme kinetics indicated that purpurogallin is a competitive inhibitor of both ATP (K i = 54.9 mM for autophosphorylation, K i = 33.9 mM for phosphorylation of exogenous substrate) and the tyrosine-containing acceptor substrate poly(glutamate, alanine, tyrosine) 6:3:1 (K i = 83.7 mM).