Genistein inhibition of fast Na+ current in uterine leiomyosarcoma cells is independent of tyrosine kinase inhibition.
Possible regulation of fast Na+ channels by tyrosine kinase was examined in human uterine smooth muscle cell line, using whole-cell voltage clamp (at a holding potential of - 90 mV). Bath application of genistein, an inhibitor tyrosine kinase, decreased the fast Na+ current (INa(f)) dose-dependently. The maximal inhibition of INa(f) was 98%, and the concentration for half-maximal inhibition (IC50) was 9 microM. The effect of genistein was rapidly reversible. Daidzein, an inactive analog of genistein, had a similar inhibitory effect on INa(f). These results suggest that the fast Na+ channels in uterine sarcoma cells may be directly blocked by genistein and daidzein, i.e., their effect may be independent of tyrosine kinase inhibition.
Kusaka
M
M
Department of Molecular and Cellular Physiology, College of Medicine, University of Cincinnati, OH 45267, USA.
Sperelakis
N
N
D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D019833:Genistein; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D007890:Leiomyosarcoma; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D026941:Sodium Channel Blockers; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D026941:Sodium Channel Blockers; C004742:daidzein; D019833:Genistein; D011505:Protein-Tyrosine Kinases