title: A robust screening method for dietary agents that activate tumour-suppressor microRNAs.
abstract: Certain dietary agents, such as natural products, have been reported to show anti-cancer effects. However, the underlying mechanisms of these substances in human cancer remain unclear. We recently found that resveratrol exerts an anti-cancer effect by upregulating tumour-suppressor microRNAs (miRNAs). In the current study, we aimed to identify new dietary products that have the ability to activate tumour-suppressor miRNAs and that therefore may serve as novel tools for the prevention and treatment of human cancers. We describe the generation and use of an original screening system based on a luciferase-based reporter vector for monitoring miR-200c tumour-suppressor activity. By screening a library containing 139 natural substances, three natural compounds - enoxolone, magnolol and palmatine chloride - were identified as being capable of inducing miR-200c expression in breast cancer cells at 10 μM. Moreover, these molecules suppressed the invasiveness of breast cancer cells in vitro. Next, we identified a molecular pathway by which the increased expression of miR-200c induced by natural substances led to ZEB1 inhibition and E-cadherin induction. These results indicate that our method is a valuable tool for a fast identification of natural molecules that exhibit tumour-suppressor activity in human cancer through miRNA activation.
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.|Department of Biological Sciences, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Luc
authors.initials: L
authors.lastname: Gailhouste
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.|Integrative Bioscience and Biomedical Engineering, Graduate School of Science and Engineering, Waseda University, 2-2 Wakamatsu, Shinjuku, Tokyo 162-8480, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yasukawa
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Kosaka
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001600:Berberine Alkaloids / Q000494:pharmacology; D001688:Biological Products / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019587:Dietary Supplements; D004354:Drug Screening Assays, Antitumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D016147:Genes, Tumor Suppressor; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017705:Lignans / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics*; D010641:Phenotype; D054852:Small Molecule Libraries; D014157:Transcription Factors / Q000235:genetics; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000970:Antineoplastic Agents; D001600:Berberine Alkaloids; D001688:Biological Products; D001713:Biphenyl Compounds; D015820:Cadherins; D018398:Homeodomain Proteins; D017705:Lignans; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D054852:Small Molecule Libraries; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; C005498:magnolol; C005413:palmatine; D006034:Glycyrrhetinic Acid