Geranylgeranylacetone Induces Apoptosis in HL-60 Cells.
- 1 January 1999
- journal article
- Published by Japan Society for Cell Biology in Cell Structure and Function
- Vol. 24 (3), 161-168
- https://doi.org/10.1247/csf.24.161
Abstract
Geranylgeranylacetone (GGA) induces apoptosis in human leukemia HL-60 cells in a dose- and time-dependent manner. This effect was completely prevented by the pan-caspase inhibitor z-Val-Ala-Asp(OMe) fluoromethylketone, thereby implicating the caspase cascade in the process. Prior to DNA fragmentation, GGA treatment markedly activated caspase-3(-like) proteases, which might be responsible for the observed apoptosis. In addition, GGA treatment interfered with the processing and membrane localization of Rap1 and Ras, and these changes may be a result of apoptosis. Moreover, nitric oxide donors significantly accentuated the GGA-induced apoptosis, suggesting that the apoptotic pathway induced by GGA might be regulated by a redox-sensitive mechanism. Taken together, these data suggest that the isoprenoid, GGA, is an effective inducer of apoptotic cell death in HL-60 cells.Keywords
This publication has 32 references indexed in Scilit:
- Mitochondria and ApoptosisScience, 1998
- Do Reactive Oxygen Species Underlie the Mechanism of Apoptosis in the Tadpole Tail?Free Radical Biology & Medicine, 1997
- Caspases: killer proteasesTrends in Biochemical Sciences, 1997
- Nitric Oxide and Some Nitric Oxide Donor Compounds Enhance the Cytotoxicity of CisplatinNitric Oxide, 1997
- Rapid Loss in the Mitochondrial Membrane Potential during Geranylgeranoic Acid-Induced ApoptosisBiochemical and Biophysical Research Communications, 1997
- Molecular Mechanisms of Apoptosis in HL-60 Cells Induced by a Nitric Oxide-Releasing CompoundFree Radical Research, 1997
- Inhibition of Isoprenoid Biosynthesis Induces Apoptosis in Human Promyelocytic HL-60 CellsBiochemical and Biophysical Research Communications, 1994
- Geranylgeranylacetone Used as an Antiulcer Agent Is a Potent Inducer of Differentiation of Various Human Myeloid Leukemia Cell LinesBiochemical and Biophysical Research Communications, 1993
- Protein Isoprenylation and Methylation at Carboxy-Terminal Cysteine ResiduesAnnual Review of Biochemistry, 1992
- Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activationNature, 1980