Cardamonin reduces chemotherapy-enriched breast cancer stem-like cells in vitro and in vivo
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Deyong Jia1, Yuan Tan1, Huijuan Liu1,2, Sarah Ooi1, Li Li1, Kathryn Wright1, Steffany Bennett1, Christina L. Addison1,3, Lisheng Wang1,4,5
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
2Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200240, China
3Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada
4Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada
5Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada
Lisheng Wang, e-mail: [email protected]
Keywords: chemotherapy, cardamonin, breast cancer stem cells, in vivo
Received: April 24, 2015 Accepted: October 06, 2015 Published: October 17, 2015
The failure of cytotoxic chemotherapy in breast cancers has been closely associated with the presence of drug resistant cancer stem cells (CSCs). Thus, screening for small molecules that selectively inhibit growth of CSCs may offer great promise for cancer control, particularly in combination with chemotherapy. In this report, we provide the first demonstration that cardamonin, a small molecule, selectively inhibits breast CSCs that have been enriched by chemotherapeutic drugs. In addition, cardamonin also sufficiently prevents the enrichment of CSCs when simultaneously used with chemotherapeutic drugs. Specifically, cardamonin effectively abolishes chemotherapeutic drug-induced up-regulation of IL-6, IL-8 and MCP-1 and activation of NF-κB/IKBα and Stat3. Furthermore, in a xenograft mouse model, co-administration of cardamonin and the chemotherapeutic drug doxorubicin significantly retards tumor growth and simultaneously decreases CSC pools in vivo. Since cardamonin has been found in some herbs, this work suggests a potential new approach for the effective treatment of breast CSCs by administration of cardamonin either concurrent with or after chemotherapeutic drugs.
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