title: Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells.
abstract: Cancer stem-like cell (CS-like cell) is considered to be responsible for recurrence and drug resistance events in breast cancer, which makes it a potential target for novel cancer therapeutic strategy. The FDA approved flubendazole, has been widely used in the treatment of intestinal parasites. Here, we demonstrated a novel effect of flubendazole on breast CS-like cells. Flubendazole inhibited breast cancer cells proliferation in dose- and time-dependent manner and delayed tumor growth in xenograft models by intraperitoneal injection. Importantly, flubendazole reduced CD44high/CD24low subpopulation and suppressed the formation of mammosphere and the expression of self-renewal related genes including c-myc, oct4, sox2, nanog and cyclinD1. Moreover, we found that flubendazole induced cell differentiation and inhibited cell migration. Consistently, flubendazole reduced mesenchymal markers (β-catenin, N-cadherin and Vimentin) expression and induced epithelial and differentiation marker (Keratin 18) expression in breast cancer cells. Mechanism study revealed that flubendazole arrested cell cycle at G2/M phase and induced monopolar spindle formation through inhibiting tubulin polymerization. Furthermore, flubendazole enhanced cytotoxic activity of conventional therapeutic drugs fluorouracil and doxorubicin against breast cancer cells. In conclusion, our findings uncovered a remarkable effect of flubendazole on suppressing breast CS-like cells, indicating a novel utilization of flubendazole in breast cancer therapy.
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.|Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Zhi-Jie
authors: ZJ
authors: Hou
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Xi
authors: X
authors: Luo
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Wei
authors: W
authors: Zhang
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Fei
authors: F
authors: Peng
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Bai
authors: B
authors: Cui
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors: Si-Jin
authors: SJ
authors: Wu
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Fei-Meng
authors: FM
authors: Zheng
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Jie
authors: J
authors: Xu
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Ling-Zhi
authors: LZ
authors: Xu
authors: Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors: Zi-Jie
authors: ZJ
authors: Long
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Xue-Ting
authors: XT
authors: Wang
authors: Department of Hematology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Guo-Hui
authors: GH
authors: Li
authors: Department of Critical Care Medicine, the First Affiliated Hospital, Dalian Medical University, Dalian, China.
authors: Xian-Yao
authors: XY
authors: Wan
authors: Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
authors: Yong-Liang
authors: YL
authors: Yang
authors: Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China.
authors: Quentin
authors: Q
authors: Liu
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008463:Mebendazole / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D011897:Random Allocation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000969:Antinematodal Agents; D000970:Antineoplastic Agents; D008463:Mebendazole; C018945:flubendazole
keywords: breast cancer; cancer stem-like cell; cell cycle; flubendazole; tubulin