Geranylgeranylacetone induces apoptosis in HL-60 cells. |
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| Authors: | S Okada M Yabuki T Kanno K Hamazaki T Yoshioka T Yasuda A A Horton K Utsumi |
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| Affiliation: | Department of Cell Chemistry, Institute of Molecular and Cell Biology, Okayama University Medical School, Japan. |
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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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