title: 11-epi-Sinulariolide acetate reduces cell migration and invasion of human hepatocellular carcinoma by reducing the activation of ERK1/2, p38MAPK and FAK/PI3K/AKT/mTOR signaling pathways.
abstract: Cancer metastasis is one of the major causes of death in cancer. An active compound, 11-epi-sinulariolide acetate (11-epi-SA), isolated from the cultured soft coral Sinularia flexibilis has been examined for potential anti-cell migration and invasion effects on hepatocellular carcinoma cells (HCC). However, the molecular mechanism of anti-migration and invasion by 11-epi-SA on HCC, along with their corresponding effects, remain poorly understood. In this study, we investigated anti-migration and invasion effects and the underlying mechanism of 11-epi-SA in HA22T cells, and discovered by trans-well migration and invasion assays that 11-epi-SA provided a concentration-dependent inhibitory effect on the migration of human HCC HA22T cells. After treatment with 11-epi-SA for 24 h, there were suppressed protein levels of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and urokinase-type plasminogen activator (uPA) in HA22T cells. Meanwhile, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and metalloproteinase-2 (TIMP-2) were increased in a concentration-dependent manner. Further investigation revealed that 11-epi-SA suppressed the phosphorylation of ERK1/2 and p38MAPK. The 11-epi-SA also suppressed the expression of the phosphorylation of FAK/PI3K/AKT/mTOR pathways.
authors.affiliation: Graduate Institute of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91202, Taiwan. q87634@hotmail.com.
authors.forename: Jen-Jie
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan. x2219@nmmba.gov.tw.
authors.forename: Jui-Hsin
authors.initials: JH
authors.lastname: Su
authors.affiliation: Kaohsiung District Agricultural Improvement Station, Pingtung 900, Taiwan. tsaicc@mail.kdais.gov.tw.
authors.forename: Chi-Chu
authors.initials: CC
authors.lastname: Tsai
authors.affiliation: Department of Physical Medicine and Rehabilitation, Kaohsiung Medical University Hospital, Kaohsiung 80761, Taiwan. chernkmu@gmail.com.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Graduate Institute of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung 91202, Taiwan. mhliao@mail.npust.edu.tw.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Liao
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: D000818:Animals; D037421:Anthozoa / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases; D019716:Tissue Inhibitor of Metalloproteinase-2
chemical_list: D004224:Diterpenes; D009363:Neoplasm Proteins; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; C050253:sinulariolide; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9