Department of Research, Pingtung Christian Hospital, Pingtung 90059, Taiwan.
Mar Drugs. 2012 Dec 18;10(12):2893-911. doi: 10.3390/md10122893.
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.
从软珊瑚 Sinularia flexibilis 中分离得到的单体化合物 sinulariolide 对 TSGH 膀胱癌细胞具有抗增殖、抗迁移和诱导凋亡的活性。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法、细胞迁移实验和流式细胞术分别确定了 sinulariolide 的抗肿瘤作用。结果表明，sinulariolide 呈剂量依赖性抑制膀胱癌细胞的生长和迁移，并通过流式细胞术诱导早期和晚期凋亡。此外，sinulariolide 诱导的细胞凋亡与线粒体介导的凋亡途径有关，这是通过线粒体膜电位丧失、细胞色素 C 释放、caspase-3/-9、Bax 和 Bad 的激活以及 Bcl-2/Bcl-xL/Mcl-1 的抑制来阐明的。PARP-1 切割产物的检测表明 caspase 非依赖性途径的部分参与。此外，抑制 p38MAPK 活性可导致 p38MAPK 通路也参与了 sinulariolide 诱导的细胞凋亡。总之，这些结果表明 sinulariolide 通过线粒体相关和 p38MAPK 通路诱导膀胱癌细胞凋亡。
