BC-02 eradicates liver cancer stem cells by upregulating the ROS-dependent DNA damage

  • Authors:
    • Chunhui Dou
    • Chunyan Fang
    • Yan Zhao
    • Xiaoyan Fu
    • Yufei Zhang
    • Dongqi Zhu
    • Huina Wu
    • Huijie Liu
    • Jian Zhang
    • Wenfang Xu
    • Zhijun Liu
    • Hongyan Wang
    • Daqi Li
    • Xuejian Wang
  • View Affiliations

  • Published online on: October 16, 2017     https://doi.org/10.3892/ijo.2017.4159
  • Pages:1775-1784
0

Abstract

Cancer stem cells (CSCs) are responsible for chemoresistance, tumor recurrence and metastasis. Reportedly, aminopeptidase N (APN, also known as CD13) is a marker for semi-quiescent CSCs and a therapeutic target in human liver CSCs. In the present study, the effect of BC-02, a compound obtained by conjugating a CD13 inhibitor bestatin and fluorouracil (5-FU), was investigated toward liver CSCs. Tumor spheres formed in serum-free culture conditions have been successfully used to enrich CSCs. In this study, the sphere cells were shown to have several characteristics of CSCs, including drug resistance, high tumorigenicity, epithelial-mesenchymal transition (EMT) phenotype, lower reactive oxygen species (ROS) levels, greater colony-forming efficiency and increased proliferation capacity in vitro. Furthermore, BC-02 effectively suppressed self-renewal and malignant proliferation of CSCs compared with 5-FU, bestatin, and even the combination of 5-FU and bestatin. In addition, cell proliferation was effectively suppressed when exposed to 5-FU plus CD13-neutralizing antibody (CD13 Ab) compared with 5-FU alone. BC-02 can effectively inhibit the activity of CD13. Results demonstrated that CD13 inhibitor BC-02 impaired the properties of liver CSCs by targeting CD13 and upregulating the intracellular ROS and ROS-induced DNA damage. BC-02 might be a potential therapeutic agent for eradicating the liver CSCs and overcoming chemoresistance in liver cancer.

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December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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Copy and paste a formatted citation
APA
Dou, C., Fang, C., Zhao, Y., Fu, X., Zhang, Y., Zhu, D. ... Wang, X. (2017). BC-02 eradicates liver cancer stem cells by upregulating the ROS-dependent DNA damage. International Journal of Oncology, 51, 1775-1784. https://doi.org/10.3892/ijo.2017.4159
MLA
Dou, C., Fang, C., Zhao, Y., Fu, X., Zhang, Y., Zhu, D., Wu, H., Liu, H., Zhang, J., Xu, W., Liu, Z., Wang, H., Li, D., Wang, X."BC-02 eradicates liver cancer stem cells by upregulating the ROS-dependent DNA damage". International Journal of Oncology 51.6 (2017): 1775-1784.
Chicago
Dou, C., Fang, C., Zhao, Y., Fu, X., Zhang, Y., Zhu, D., Wu, H., Liu, H., Zhang, J., Xu, W., Liu, Z., Wang, H., Li, D., Wang, X."BC-02 eradicates liver cancer stem cells by upregulating the ROS-dependent DNA damage". International Journal of Oncology 51, no. 6 (2017): 1775-1784. https://doi.org/10.3892/ijo.2017.4159