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      Identification of Selective Inhibitors of Cancer Stem Cells by High-Throughput Screening

      , , , , , ,
      Cell
      Elsevier BV

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          Abstract

          Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          00928674
          August 2009
          August 2009
          : 138
          : 4
          : 645-659
          Article
          10.1016/j.cell.2009.06.034
          19682730
          54146530-811d-4fd3-82ac-e1678cdacd53
          © 2009

          https://www.elsevier.com/tdm/userlicense/1.0/

          https://www.elsevier.com/open-access/userlicense/1.0/

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