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Cell DOI:10.1016/j.cell.2009.06.034

Identification of selective inhibitors of cancer stem cells by high-throughput screening.

Publication TypeJournal Article
Year of Publication2009
AuthorsGupta, PB, Onder, TT, Jiang, G, Tao, K, Kuperwasser, C, Weinberg, RA, Lander, ES
Date Published2009 Aug 21
KeywordsAnimals, Antineoplastic Agents, Apoptosis, Cell Line, Tumor, Drug Resistance, Neoplasm, Drug Screening Assays, Antitumor, Gene Expression Regulation, Neoplastic, Humans, Mammary Neoplasms, Experimental, Mice, Mice, Inbred BALB C, Mice, Inbred NOD, Mice, SCID, Neoplasm Metastasis, Neoplasm Transplantation, Neoplastic Stem Cells, Paclitaxel, Pyrans

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.


Alternate JournalCell
PubMed ID19682730
PubMed Central IDPMC4892125
Grant ListR03 MH089663 / MH / NIMH NIH HHS / United States