The cell competition-based high-throughput screening identifies small compounds that promote the elimination of RasV12-transformed cells from epithelia

Sci Rep. 2015 Oct 20:5:15336. doi: 10.1038/srep15336.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbazoles / pharmacology
  • Cell Communication / drug effects
  • Cell Death / drug effects
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Transformation, Neoplastic / genetics*
  • Drug Screening Assays, Antitumor*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism*
  • Genes, ras*
  • High-Throughput Screening Assays*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • Small Molecule Libraries*


  • Carbazoles
  • Small Molecule Libraries
  • rebeccamycin