2007 年 30 巻 5 号 p. 880-884
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 Ca2+ 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 Ca2+ and the corresponding decrease in intracellular pH are required for the induction of apoptosis in HL60 cells by GGO.