Geranylgeranylacetone Induces Apoptosis in HL-60 Cells

Shohei Okada; Munehisa Yabuki; Tomoko Kanno; Keisuke Hamazaki; Tamotsu Yoshioka; Tatsuji Yasuda; Alan A. Horton; Kozo Utsumi

doi:10.1247/csf.24.161

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Geranylgeranylacetone Induces Apoptosis in HL-60 Cells

Shohei Okada, Munehisa Yabuki, Tomoko Kanno, Keisuke Hamazaki, Tamotsu Yoshioka, Tatsuji Yasuda, Alan A. Horton, Kozo Utsumi

Author information

Shohei Okada
Department of Cell Chemistry, Institute of Molecular and Cell Biology, Okayama University Medical School, Okayama 700-8558, Japan
Munehisa Yabuki
Institute of Medical Science, Kurashiki Medical Center, Kurashiki 710-8522, Japan
Tomoko Kanno
Institute of Medical Science, Kurashiki Medical Center, Kurashiki 710-8522, Japan
Keisuke Hamazaki
Institute of Medical Science, Kurashiki Medical Center, Kurashiki 710-8522, Japan
Tamotsu Yoshioka
Institute of Medical Science, Kurashiki Medical Center, Kurashiki 710-8522, Japan
Tatsuji Yasuda
Department of Cell Chemistry, Institute of Molecular and Cell Biology, Okayama University Medical School, Okayama 700-8558, Japan
Alan A. Horton
School of Biochemistry, University of Birmingham, Edgebaston, Birmingham B15 2TT, United Kingdom
Kozo Utsumi
Institute of Medical Science, Kurashiki Medical Center, Kurashiki 710-8522, Japan

Keywords: geranylgeranylacetone, isoprenoid, apoptosis, HL-60 cell, caspase, isoprenylation, nitric oxide

JOURNAL FREE ACCESS

1999 Volume 24 Issue 3 Pages 161-168

DOI https://doi.org/10.1247/csf.24.161

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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.

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