Induction of apoptosis by sinulariolide from soft coral through mitochondrial-related and p38MAPK pathways on human bladder carcinoma cells.

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.

• Authors: Choo-Aun Neoh, Robert Y-L Wang, Zhong-Hao Din, Jui-Hsin Su, Yu-Kuei Chen, Feng-Jen Tsai, Shun-Hsiang Weng, Yu-Jen Wu
• Journal: Marine drugs (Mar Drugs) Vol. 10 Issue 12 Pg. 2893-911 (Dec 18 2012) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 23249971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Diterpenes
• sinulariolide
• Cytochromes c
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anthozoa (chemistry)
• Antineoplastic Agents (administration & dosage, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cytochromes c (metabolism)
• Diterpenes (administration & dosage, isolation & purification, pharmacology)
• Dose-Response Relationship, Drug
• Flow Cytometry
• Humans
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Time Factors
• Urinary Bladder Neoplasms (drug therapy, pathology)
• p38 Mitogen-Activated Protein Kinases (metabolism)