Effects of the tyrosine-kinase inhibitor genistein on DNA synthesis and phospholipid-derived second messenger generation in mouse 10T1/2 fibroblasts and rat liver T51B cells .

Dean NM ; Kanemitsu M ; Boynton AL

Cancer Research Center of Hawaii , University of Hawaii , Honolulu 96813 .

Biochem Biophys Res Commun 165 : 795-801 ( 1989)

Abstract
We have examined the effects of the tyrosine kinase inhibitor genistein on hormone dependent cell proliferation and intracellular signalling in mouse 10T1/2 fibroblasts and rat liver T51B epithelial cells . Genistein inhibits both PDGF and EGF induced mitogenesis with an IC50 of 40 uM and 10 uM respectively . Genistein also inhibits inositol phosphate generation and calcium signalling in response to PDGF , and , 2-diacylglycerol generation and calpactin II translocation in response to EGF . By contrast genistein does not inhibit inositol phosphate production , Ca2+ signalling or 1,2-diacylglycerol generation in response to ATP or angiotensin II . These data demonstrate that genistein selectively inhibits tyrosine kinase dependent processes without effecting similar responses obtained to hormones which are not dependent upon tyrosine kinase activation .