title: Increase in intracellular Ca(2+) concentrations and the corresponding intracellular acidification are early steps for induction of apoptosis by geranylgeraniol in HL60 cells.
abstract: To elucidate the mechanism of induction of apoptosis by geranylgeraniol (GGO), which is a potent inducer of apoptosis in various lines of human cancer cells, we examined the role of intracellular acidification during GGO-induced apoptosis using human leukemia HL60 cells. Flow cytometry analysis revealed that apoptosis induced in human leukemia HL60 cells by GGO was associated with intracellular acidification. Both GGO-induced intracellular acidification and apoptosis as analyzed by DNA fragmentation were inhibited by phorbol myristate acetate (TPA) and O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N-tetraacetic acid tetraacetoxymethyl ester (BAPTA-AM), an intracellular Ca(2+) chelator, but not by ethyleneglycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA). These results suggest that the early concentration change of intracellular Ca(2+) and the corresponding decrease in intracellular pH are required for the induction of apoptosis in HL60 cells by GGO.
authors.affiliation: Laboratory of Biological Chemistry, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Masuda
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Aiuchi
authors.forename: Saori
authors.initials: S
authors.lastname: Mihara
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakajo
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Nakaya
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004224:Diterpenes; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D045304:Cytochromes c; C017338:geranylgeraniol; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium