title: The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia.
abstract: Recent studies have revealed that cell competition can occur between normal and transformed epithelial cells; normal epithelial cells recognize the presence of the neighboring transformed cells and actively eliminate them from epithelial tissues. Here, we have established a brand-new high-throughput screening platform that targets cell competition. By using this platform, we have identified Rebeccamycin as a hit compound that specifically promotes elimination of RasV12-transformed cells from the epithelium, though after longer treatment it shows substantial cytotoxic effect against normal epithelial cells. Among several Rebeccamycin-derivative compounds, we have found that VC1-8 has least cytotoxicity against normal cells but shows the comparable effect on the elimination of transformed cells. This cell competition-promoting activity of VC1-8 is observed both in vitro and ex vivo. These data demonstrate that the cell competition-based screening is a promising tool for the establishment of a novel type of cancer preventive medicine.
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Sapporo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yamauchi
authors.affiliation: Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsumaru
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Sapporo, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Morita
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Sapporo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.|Laboratory of Biomolecular Science, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.affiliation: Hokkaido University Graduate School of Information Science and Technology, Sapporo, Japan.
authors.forename: Ichigaku
authors.initials: I
authors.lastname: Takigawa
authors.affiliation: Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.|Division of Gene Function Analysis, Translational Research Center, Fukushima Medical University, Fukushima, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Semba
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Sapporo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kon
authors.affiliation: Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University Graduate School of Chemical Sciences and Engineering, Sapporo, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Fujita
mesh_terms: D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D011905:Genes, ras; D057166:High-Throughput Screening Assays; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D054852:Small Molecule Libraries
chemical_list: D002227:Carbazoles; D054852:Small Molecule Libraries; C053339:rebeccamycin