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Mar. Drugs 2012, 10(12), 2893-2911; doi:10.3390/md10122893
Article

Induction of Apoptosis by Sinulariolide from Soft Coral through Mitochondrial-Related and p38MAPK Pathways on Human Bladder Carcinoma Cells

1,†
,
2,†
,
3
,
4
,
5
,
6
,
7
 and
6,*
1 Department of Research, Pingtung Christian Hospital, Pingtung 90059, Taiwan 2 Department of Biomedical Sciences and Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 33302, Taiwan 3 Graduate Institute of Applied Healthy and Biotechnology, Meiho University, Pingtung 91202, Taiwan 4 National Museum of Marine Biology and Aquarium, Pingtung 94446, Taiwan 5 Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan 6 Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan 7 Department of Hospitality Management, Meiho University, Pingtung 91202, Taiwan These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 29 September 2012 / Revised: 30 November 2012 / Accepted: 12 December 2012 / Published: 18 December 2012
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Abstract

Sinulariolide, an isolated compound from the soft coral Sinularia flexibilis, possesses the anti-proliferative, anti-migratory and apoptosis-inducing activities against the TSGH bladder carcinoma cell. The anti-tumor effects of sinulariolide were determined by 3-(4,5-cimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, cell migration assay and flow cytometry, respectively. Sinulariolide inhibited the growth and migration of bladder carcinoma cells in a dose-dependent manner, as well as induced both early and late apoptosis as determined by the flow cytometer. Also, the sinulariolide-induced apoptosis is related to the mitochondrial-mediated apoptosis via caspase-dependent pathways, elucidated by the loss of mitochondrial membrane potential, release of cytochrome C, activation of caspase-3/-9, Bax and Bad, as well as suppression of Bcl-2/Bcl-xL/Mcl-1. Detection of the PARP-1 cleaved product suggested the partial involvement of caspase-independent pathways. Moreover, inhibition of p38MAPK activity leads to the rescue of the cell cytotoxicity of sinulariolide-treated TSGH cells, indicating that the p38MAPK pathway is also involved in the sinulariolide-induced cell apoptosis. Altogether, these results suggest that sinulariolide induces apoptosis against bladder cancer cells through mitochondrial-related and p38MAPK pathways.
Keywords: sinulariolide; bladder cancer cells; mitochondrial-related pathways sinulariolide; bladder cancer cells; mitochondrial-related pathways
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Neoh, C.-A.; Wang, R.Y.-L.; Din, Z.-H.; Su, J.-H.; Chen, Y.-K.; Tsai, F.-J.; Weng, S.-H.; Wu, Y.-J. Induction of Apoptosis by Sinulariolide from Soft Coral through Mitochondrial-Related and p38MAPK Pathways on Human Bladder Carcinoma Cells. Mar. Drugs 2012, 10, 2893-2911.

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