Geranylgeraniol potently induces caspase-3-like activity during apoptosis in human leukemia U937 cells.

Abstract

In a previous study, we showed that geranylgeraniol (GGO) is a potent inducer of apoptosis in human leukemia cells. The present study describes the effects of GGO on the activity of cysteine-dependent aspartate-directed proteases (caspases) in human leukemia U937 cells. The caspase-3 (CPP32) activity was increased in a time-dependent manner by treatment with 50 microM GGO, whereas no activation of caspase-1 (interleukin-1beta converting enzyme (ICE)) was observed in any time period under the same experimental conditions. Other isoprenyl compounds such as geraniol, geranylgerany-lacetone, and vitamin K2 had no measurable effects on the activities of either caspase-3 or caspase-1. A inhibitor that preferentially inhibits the caspase-3 related caspases, Z-DEVD-FMK, strongly blocked the GGO-induced DNA fragmentation. These results suggest the involvement of caspase-3 in GGO-induced apoptosis in U937 human leukemia cells.

• Authors: Y Masuda, M Nakaya, S Nakajo, K Nakaya
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 234 Issue 3 Pg. 641-5 (May 29 1997) ISSN: 0006-291X [Print] United States
• PMID: 9175767 (Publication Type: Journal Article)

Chemical References

• Diterpenes
• geranylgeraniol
• CASP3 protein, human
• Caspase 3
• Caspases
• Cysteine Endopeptidases
• Tetradecanoylphorbol Acetate

Topics

• Apoptosis
• Caspase 3
• Caspases
• Cysteine Endopeptidases (biosynthesis)
• Diterpenes (pharmacology)
• Enzyme Induction
• Humans
• Leukemia (enzymology, pathology)
• Tetradecanoylphorbol Acetate (pharmacology)
• Tumor Cells, Cultured