Oncotarget

Research Papers:

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 and Quentin Liu _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:6326-6340. https://doi.org/10.18632/oncotarget.3436

Metrics: PDF 1781 views  |   HTML 2713 views  |   ?  


Abstract

Zhi-Jie Hou1,*, Xi Luo1,*, Wei Zhang1,*, Fei Peng1, Bai Cui1, Si-Jin Wu2, Fei-Meng Zheng1, Jie Xu1, Ling-Zhi Xu1, Zi-Jie Long3, Xue-Ting Wang1, Guo-Hui Li4, Xian-Yao Wan5, Yong-Liang Yang2 and Quentin Liu1

1 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

2 Center for Molecular Medicine, School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China

3 Department of Hematology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

4 Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian, China

5 Department of Critical Care Medicine, the First Affiliated Hospital, Dalian Medical University, Dalian, China

* These authors contributed equally to this work

Correspondence to:

Quentin Liu, email:

Yong-liang Yang, email:

Xian-Yao Wan, email:

Keywords: flubendazole, breast cancer, cancer stem-like cell, cell cycle, tubulin

Received: August 23, 2014 Accepted: January 05, 2015 Published: January 21, 2015

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 3436