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
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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.
Neoh C-A, Wang RY-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. Marine Drugs. 2012; 10(12):2893-2911.
Neoh, Choo-Aun; Wang, Robert Y.-L.; Din, Zhong-Hao; Su, Jui-Hsin; Chen, Yu-Kuei; Tsai, Feng-Jen; Weng, Shun-Hsiang; Wu, Yu-Jen. 2012. "Induction of Apoptosis by Sinulariolide from Soft Coral through Mitochondrial-Related and p38MAPK Pathways on Human Bladder Carcinoma Cells." Mar. Drugs 10, no. 12: 2893-2911.