geranylgeranylacetone and Melanoma

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.

Topics: Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Cell Survival; Diterpenes; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Melanoma; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Tumor Suppressor Protein p53