Flubendazole, FDA-approved anthelmintic, targets breast cancer stem-like cells

Zhi Jie Hou, Xi Luo, Wei Zhang, Fei Peng, Bai Cui, Si Jin Wu, Fei Meng Zheng, Jie Xu, Ling Zhi Xu, Zi Jie Long, Xue Ting Wang, Guo Hui Li, Xian Yao Wan, Yong Liang Yang, Quentin Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6326-6340
Number of pages15
JournalOncotarget
Volume6
Issue number8
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Breast cancer
  • Cancer stem-like cell
  • Cell cycle
  • Flubendazole
  • Tubulin

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