Activation of chloride secretion by isoflavone genistein in endometrial epithelial cells

Abstract

Background/Aim: Genistein, the most active isoflavone found primarily in soybeans, alters ion transport functions in intestinal and airway epithelia. The present study aims to investigate the acute effects and mechanisms of action of genistein in immortalized porcine endometrial epithelial cells. Methods: Ussing chamber technique was used for transepithelial electrical measurements. Results: Genistein increased short-circuit currents (I sc ) which were inhibited by glibenclamide, NPPB, CFTRinh-172, DIDS or bumetanide, but not amiloride. In experiments with amphotericin B-permeabilized monolayers, genistein activated the apical Cl - current and barium-sensitive basolateral K + current while inhibiting the apical K + current. Genistein failed to increase the I sc in the presence of forskolin or IBMX, but did increase the I sc in UTP. Pretreatment with genistein also abolished the increase in the I sc when induced by forskolin, IBMX or UTP. However, Ca 2+ -chelating BAPTA-AM did not affect the genistein-induced increase in the I sc . The genistein-stimulated I sc was reduced by tyrosine kinase inhibitors, tyrphostin A23 or AG490. However, vanadate, a tyrosine phosphatase inhibitor, failed to inhibit the genistein response. Estrogen receptor antagonist ICI182,780 did not alter the genistein's action. Conclusion: The soy isoflavone, genistein, stimulates Cl - secretion in endometrial epithelial cells possibly via a direct activation of CFTR which appears to be modulated through a tyrosine kinase-dependent pathway. The present findings may be of benefit for the therapeutic application of genistein in the treatment of electrolyte transport disorders in the epithelia. © 2013 S. Karger AG, Basel.