Geranylgeranylacetone induces apoptosis via the intrinsic pathway in human melanoma cells

Biomed Pharmacother. 2016 Aug:82:15-9. doi: 10.1016/j.biopha.2016.04.051. Epub 2016 May 3.

Abstract

The aim of this study was to test the anti-cancer effects of geranylgeranylacetone (GGA), an isoprenoid compound, on human melanoma cells. Human melanoma cell lines G361, SK-MEL-2, and SK-MEL-5 were treated with GGA at various doses (1-100μM). Cell viability was measured by crystal violet assay. Western blot analysis was adopted to detect marker proteins of apoptosis. GGA significantly reduced the viability of G361, SK-MEL-2, and SK-MEL-5 human melanoma cells at concentrations above 10μM. Western blot analysis showed the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) after GGA treatment, as well as activation of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP) cleavage. GGA also induced p53 and Bax expression, but did not affect expression of Bcl-2 and MITF. These findings suggest that GGA induces apoptosis through the intrinsic pathway. Accordingly, GGA should be considered for further development as a potential agent for melanoma.

Keywords: Apoptosis; Caspase; Geranylgeranylacetone; Melanoma; Skin cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diterpenes / pharmacology*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / drug effects
  • Melanoma / enzymology
  • Melanoma / pathology*
  • Signal Transduction / drug effects*
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Diterpenes
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • geranylgeranylacetone