Geranylgeranylacetone induces apoptosis in HL-60 cells

Cell Struct Funct. 1999 Jun;24(3):161-8. doi: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis*
  • Blotting, Western
  • Caspases / metabolism
  • DNA Fragmentation
  • DNA-Binding Proteins / metabolism
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • HL-60 Cells / drug effects*
  • HL-60 Cells / metabolism
  • Humans
  • Multigene Family
  • Nitroso Compounds / pharmacology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Subcellular Fractions / metabolism
  • bcl-2-Associated X Protein
  • ras Proteins / metabolism

Substances

  • Amino Acid Chloromethyl Ketones
  • DNA-Binding Proteins
  • Diterpenes
  • NOC 18
  • Nitroso Compounds
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Caspases
  • ras Proteins
  • geranylgeranylacetone