title: Glibenclamide induces apoptosis through inhibition of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels and intracellular Ca(2+) release in HepG2 human hepatoblastoma cells.
abstract: Glibenclamide, an inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channels, induced apoptosis in a dose- and time-dependent manner in HepG2 human hepatoblastoma cells. Glibenclamide increased intracellular Ca(2+) concentration, which was significantly inhibited by Ca(2+) release blockers dantrolene and TMB-8. BAPTA/AM, an intracellular Ca(2+) chelator, and the Ca(2+) release blockers significantly inhibited glibenclamide-induced apoptosis. Glibanclamide also increased intracellular Cl(-) concentration, which was significantly blocked by CFTR Cl(-) channel activators levamisole and bromotetramisole. These activators also significantly inhibited both intracellular Ca(2+) release and apoptosis induced by glibenclamide. The expression of CFTR protein in the cells was confirmed by Western blot analysis. These results suggest that glibenclamide induced apoptosis through inhibition of CFTR Cl(-) channels and intracellular Ca(2+) release and that this protein may be a good target for treatment of human hepatomas.
authors.affiliation: College of Pharmacy, Yeungnam University, Kyongsan, 712-749, Korea.
authors.forename: J A
authors.initials: JA
authors.lastname: Kim
authors.forename: Y S
authors.initials: YS
authors.lastname: Kang
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.forename: E H
authors.initials: EH
authors.lastname: Lee
authors.forename: B H
authors.initials: BH
authors.lastname: Yoo
authors.forename: Y S
authors.initials: YS
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D053938:DNA Fragmentation; D003620:Dantrolene / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D015870:Gene Expression; D005905:Glyburide / Q000494:pharmacology*; D018197:Hepatoblastoma; D006801:Humans; D007978:Levamisole / Q000494:pharmacology; D008113:Liver Neoplasms; D015221:Potassium Channels / Q000187:drug effects; D015398:Signal Transduction; D013773:Tetramisole / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D015221:Potassium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007978:Levamisole; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C006226:4-bromotetramisole; D013773:Tetramisole; D003620:Dantrolene; D005905:Glyburide; D002118:Calcium