title: Sinularin Induces Apoptosis through Mitochondria Dysfunction and Inactivation of the pI3K/Akt/mTOR Pathway in Gastric Carcinoma Cells.
abstract: Sinularin is an active compound isolated from the cultured soft coral Sinularia flexibilis. In this study, we investigated the effects of sinularin on two human gastric cancer cell lines, AGS and NCI-N87. Our results demonstrated that sinularin suppressed the proliferation of gastric cancer cells in a dose-dependent manner and induced apoptosis. In addition, the loss of mitochondrial membrane potential, the release of cytochrome C, the activation of Bax, Bad and caspase-3/9, and the suppression of p-Bad, Bcl-xL and Bcl-2 were observed in the cells treated with sinularin. This finding suggests that sinularin-induced apoptosis is associated with mitochondria-mediated apoptosis and occurs through caspase-dependent pathways. Furthermore, sinularin inhibited the phosphoinositol 3-kinase/Akt/mechanistic target of the rapamycin signaling pathway. Taken together, our results show that sinularin-induced apoptosis is mediated by activation of the caspase cascade and mitochondrial dysfunction. Our findings suggest that sinularin merits further evaluation as a chemotherapeutic agent for human gastric cancer.
authors.affiliation: Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan. x00002180@meiho.edu.tw.|Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan. x00002180@meiho.edu.tw.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Wu
authors.affiliation: Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan. a094162@mail.tsmh.org.tw.
authors.forename: Bing-Sang
authors.initials: BS
authors.lastname: Wong
authors.affiliation: Yu Jun Biotechnology Co., Ltd., Kaoshiun 91202, Taiwan. a714825936@gmail.com.
authors.forename: Shu-Hao
authors.initials: SH
authors.lastname: Yea
authors.affiliation: Department of Nursing, Meiho University, Pingtung 91202, Taiwan. x00002177@meiho.edu.tw.
authors.forename: Chi-I
authors.initials: CI
authors.lastname: Lu
authors.affiliation: Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan. x00009520@meiho.edu.tw.
authors.forename: Shun-Hsiang
authors.initials: SH
authors.lastname: Weng
mesh_terms: D000818:Animals; D037421:Anthozoa / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053148:Caspase 3; D053453:Caspase 9; D004224:Diterpenes; D006575:Heterocyclic Compounds, 3-Ring; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C574383:sinularin; C546842:MTOR protein, human; C494918:AKT1 protein, human; C505407:CASP3 protein, human; C506433:CASP9 protein, human
keywords: apoptosis; gastric cancer; mitochondrial dysfunction; sinularin