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

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 (IC50 = 27.5 microM) and phosphorylation of an exogenous substrate (IC50 = 45.3 microM). An examination of enzyme kinetics indicated that purpurogallin is a competitive inhibitor of both ATP (Ki = 54.9 microM for autophosphorylation, Ki = 33.9 microM for phosphorylation of exogenous substrate) and the tyrosine-containing acceptor substrate poly(glutamate, alanine, tyrosine) 6:3:1 (Ki = 83.7 microM).