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: Yutaka Masuda, Toshihiro Aiuchi, Saori Mihara, Shigeo Nakajo, Kazuyasu Nakaya
• Journal: Biological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 30 Issue 5 Pg. 880-4 (May 2007) ISSN: 0918-6158 [Print] Japan
• PMID: 17473429 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
• Egtazic Acid
• Cytochromes c
• geranylgeraniol
• Tetradecanoylphorbol Acetate
• Calcium

Topics

• Apoptosis (drug effects)
• Calcium (metabolism)
• Cytochromes c (metabolism)
• DNA Fragmentation (drug effects)
• Diterpenes (pharmacology)
• Egtazic Acid (analogs & derivatives, pharmacology)
• HL-60 Cells
• Humans
• Hydrogen-Ion Concentration
• Mitochondria (metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)