研究珊瑚萃取物sinulariolide 藉由粒腺體失調對皮膚癌細胞產生毒殺作用之影響

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题名:	研究珊瑚萃取物sinulariolide 藉由粒腺體失調對皮膚癌細胞產生毒殺作用之影響
作者:	吳裕仁
贡献者:	健康暨護理學院
关键词:	melanoma;sinulariolide;proteomic;mitochondrial;apoptosis;caspase
日期:	2012
上传时间:	2013-06-17T01:02:07Z (UTC)
摘要:	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.
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