Increase in Intracellular Ca^<2+> Concentrations and the Corresponding Intracellular Acidification Are Early Steps for Induction of Apoptosis by Geranylgeraniol in HL60 Cells(Molecular and Cell Biology)

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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.
公益社団法人日本薬学会の論文
2007-05-01