Geranylgeranylacetone induces apoptosis in HL-60 cells.
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.
Okada
S
S
Department of Cell Chemistry, Institute of Molecular and Cell Biology, Okayama University Medical School, Japan.
Yabuki
M
M
Kanno
T
T
Hamazaki
K
K
Yoshioka
T
T
Yasuda
T
T
Horton
A A
AA
Utsumi
K
K
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018922:HL-60 Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D005810:Multigene Family; D009603:Nitroso Compounds / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D051028:bcl-2-Associated X Protein; D018631:ras Proteins / Q000378:metabolism
D000590:Amino Acid Chloromethyl Ketones; D004268:DNA-Binding Proteins; D004224:Diterpenes; C093285:NOC 18; D009603:Nitroso Compounds; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases; D018631:ras Proteins; C031049:geranylgeranylacetone