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

Marine Drugs

Choo-Aun Neoh³  Robert Y.-L. Wang⁷  Zhong-Hao Din¹  Jui-Hsin Su⁵  Yu-Kuei Chen⁶  Feng-Jen Tsai⁴  Shun-Hsiang Weng² 

[1] Graduate Institute of Applied Healthy and Biotechnology, Meiho University, Pingtung 91202, Taiwan; E-Mail:;Department of Hospitality Management, Meiho University, Pingtung 91202, Taiwan; E-Mail:;Department of Research, Pingtung Christian Hospital, Pingtung 90059, Taiwan; E-Mail:;Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan; E-Mail:;National Museum of Marine Biology and Aquarium, Pingtung 94446, Taiwan; E-Mail:;Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan; E-Mail:;Department of Biomedical Sciences and Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan 33302, Taiwan; E-Mail:

关键词: sinulariolide;    bladder cancer cells;    mitochondrial-related pathways;   

DOI  :  10.3390/md10122893

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.