title: 13-acetoxysarcocrassolide induces apoptosis on human gastric carcinoma cells through mitochondria-related apoptotic pathways: p38/JNK activation and PI3K/AKT suppression.
abstract: 13-acetoxysarcocrassolide (13-AC), an active compound isolated from cultured Formosa soft coral Sarcophyton crassocaule, was found to possess anti-proliferative and apoptosis-inducing activities against AGS (human gastric adenocarcinoma cells) gastric carcinoma cells. The anti-tumor effects of 13-AC were determined by MTT assay, colony formation assessment, cell wound-healing assay, TUNEL/4,6-Diamidino-2-phenylindole (DAPI) staining, Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry. 13-AC inhibited the growth and migration of gastric carcinoma cells in a dose-dependent manner and induced both early and late apoptosis as assessed by flow cytometer analysis. 13-AC-induced apoptosis was confirmed through observation of a change in ΔΨm, up-regulated expression levels of Bax and Bad proteins, down-regulated expression levels of Bcl-2, Bcl-xl and Mcl-1 proteins, and the activation of caspase-3, caspase-9, p38 and JNK. Furthermore, inhibition of p38 and JNK activity by pretreatment with SB03580 (a p38-specific inhibitor) and SP600125 (a JNK-specific inhibitor) led to rescue of the cell cytotoxicity of 13-AC-treated AGS cells, indicating that the p38 and the JNK pathways are also involved in the 13-AC-induced cell apoptosis. Together, these results suggest that 13-AC induces cell apoptosis against gastric cancer cells through triggering of the mitochondrial-dependent apoptotic pathway as well as activation of the p38 and JNK pathways.
authors.affiliation: Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan. a081001@mail.tsmh.org.tw.
authors.forename: Ching-Chyuan
authors.initials: CC
authors.lastname: Su
authors.affiliation: Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan. yifuc@kmu.edu.tw.
authors.forename: Jeff Yi-Fu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Applied Healthy and Biotechnology, Meiho University, Pingtung 91202, Taiwan. nmm10023@yahoo.com.tw.
authors.forename: Zhong-Hao
authors.initials: ZH
authors.lastname: Din
authors.affiliation: National Museum of Marine Biology and Aquarium, Pingtung 94446, Taiwan. x2219@nmmba.gov.tw.
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.affiliation: Graduate Institute of Food Science, National Pingtung University of Science and Technology, Pingtung 91202, Taiwan. vian10045@gmail.com.
authors.forename: Zih-Yan
authors.initials: ZY
authors.lastname: Yang
authors.affiliation: Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. chernkmu@gmail.com.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Biomedical Sciences and Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. yuwang@mail.cgu.edu.tw.
authors.forename: Robert Y L
authors.initials: RY
authors.lastname: Wang
authors.affiliation: Department of Beauty Science, Meiho University, Pingtung 91202, Taiwan. wyr924@ms24.hinet.net.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002277:Carcinoma / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013274:Stomach Neoplasms / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C573067:13-acetoxysarcocrassolide; D004224:Diterpenes; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9