Sinulariolide is an active compound isolated from the cultured soft coral Sinularia
flexibilis. In this study, we investigate the effects of sinulariolide on A375 melanoma cell
growth and protein expression. Sinulariolide suppressed the proliferation and migration
of melanoma cells in a concentration-dependent manner and induced both early and
late apoptosis by the flow cytometric analysis. Comparative proteomic analysis was
conducted to investigate the effects of sinulariolide at the molecular level by
comparison between the protein profiling of melanoma cells treated with sinulariolide
and that without the treatment. The 2-DE master maps of control and treated A375 cells
were generated by analysis with the PDQuest software. The comparison between such
maps showed up- and down-regulation of 23 proteins, of which 7 were up-regulated and
16 were down-regulated. The proteomics studies described here have identified some
proteins, which are involved in the mitochondrial dysfunction and apoptosis-associated
proteins including heat shock protein 60, heat shock protein beta-1, ubiquinol
cytochrome c reductase complex core protein 1, isocitrate dehydrogenase [NAD]
subunit alpha (down-regulated), and prohibitin (up-regulated) in A375 melanoma
cells exposed to sinulariolide. Sinulariolide-induced apoptosis is relevant to the
mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the
loss of mitochondrial membrane potential, release of cytochrome c, activation of Bax ,
Bad and caspase-3/-9 as well as suppression of p-Bad, Bcl-xL and Bcl-2. Taken
together, our results showed that sinulariolide-induced apoptosis might be related to
the activation of caspase cascade and mitochondria dysfunction pathways. Our results
suggest that sinulariolide merits further evaluated as a chemotherapeutic agent for
human melanoma.
