title: 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.affiliation: Department of Research, Pingtung Christian Hospital, Pingtung 90059, Taiwan.
authors.forename: Choo-Aun
authors.initials: CA
authors.lastname: Neoh
authors.forename: Robert Y-L
authors.initials: RY
authors.lastname: Wang
authors.forename: Zhong-Hao
authors.initials: ZH
authors.lastname: Din
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.forename: Yu-Kuei
authors.initials: YK
authors.lastname: Chen
authors.forename: Feng-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Shun-Hsiang
authors.initials: SH
authors.lastname: Weng
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; C050253:sinulariolide; D045304:Cytochromes c; D048051:p38 Mitogen-Activated Protein Kinases