Activation of CFTR by genistein in human airway epithelial cell lines.
Cystic fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel expressed in epithelial cells. The effects of genistein and 4-phenylbutyrate (PBA) on CFTR were studied in three human airway epithelial cell lines expressing wild-type or DeltaF508 CFTR: Calu-3, CFSMEo-, and CFBE41o- cells. The cells were loaded with the fluorescent dye N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) and chloride efflux was studied. Forskolin and 3-isobutyl-1-methylxanthine (IBMX) induced chloride efflux in Calu-3 cells but not in CF lines. Genistein (2.5-50 microM) alone was able to induce chloride efflux in all cell lines. Genistein did not enhance the effect of forskolin and IBMX. PBA had little or no effect on genistein-induced chloride efflux. The effect of genistein seen at low concentrations makes genistein interesting for possible pharmacological treatment of CF, since it is known that similar concentrations can be obtained in plasma by a soy-rich diet.
Andersson
Charlotte
C
Department of Medical Cell Biology, University of Uppsala, Sweden.
Servetnyk
Zhanna
Z
Roomans
Godfried M
GM
D002460:Cell Line; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D010654:Phenylbutyrates / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000378:metabolism*
C505032:CFTR protein, human; D002712:Chlorides; D010654:Phenylbutyrates; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C075773:4-phenylbutyric acid; D019833:Genistein