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.
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 1,2-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.
Dean
N M
NM
Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.
Kanemitsu
M
M
Boynton
A L
AL
D000818:Animals; D017302:Annexins; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects*; D004075:Diglycerides / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D019833:Genistein; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010743:Phospholipids / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects*
D017302:Annexins; D002135:Calcium-Binding Proteins; D004075:Diglycerides; D005419:Flavonoids; D007295:Inositol Phosphates; D007529:Isoflavones; D008565:Membrane Proteins; D010743:Phospholipids; D010982:Platelet-Derived Growth Factor; D007294:Inositol; D004815:Epidermal Growth Factor; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D002118:Calcium