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

• Yamauchi, Hajime

• Matsumaru, Takanori

• Morita, Tomoko

• Ishikawa, Susumu

• Maenaka, Katsumi

• Takigawa, Ichigaku

• Semba, Kentaro

• Kon, Shunsuke

• Fujita, Yasuyuki

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.

Journal

• Scientific reports

  Scientific reports 5 15336-, 2015-10-21

  Nature Publishing Group

Keywords

• Multidisciplinary

Details

• CRID: 1050001202927744768
• NII Article ID: 120005674073
• DOI: 10.1038/srep15336
• HANDLE: 2115/60284
• ISSN: 20452322
• Web Site: https://www.nature.com/articles/srep15336.pdf
• Web Site: https://www.nature.com/articles/srep15336
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN