Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance

  • Authors:
    • Bao-Yuan Huang
    • Yu Zeng
    • Ying-Jie Li
    • Xiao-Jun Huang
    • Nan Hu
    • Nan Yao
    • Min-Feng Chen
    • Zai-Gang Yang
    • Zhe-Sheng Chen
    • Dong-Mei Zhang
    • Chang-Qing Zeng
  • View Affiliations

  • Published online on: May 17, 2017     https://doi.org/10.3892/ijo.2017.4005
  • Pages: 257-268
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Abstract

The overexpression of ATP-binding cassette (ABC) transporters is the main cause of cancer multidrug resistance (MDR), which leads to chemotherapy failure. Uncaria alkaloids are the major active components isolated from uncaria, which is a common Chinese herbal medicine. In this study, the MDR-reversal activities of uncaria alkaloids, including rhynchophylline, isorhynchophylline, corynoxeine, isocorynoxeine (Icory), hirsutine and hirsuteine, were screened; they all exhibited potent reversal efficacy when combined with doxorubicin. Among them, Icory significantly sensitized ABCB1-overexpressing HepG2/ADM and MCF-7/ADR cells to vincristine, doxorubicin and paclitaxel, but not to the non-ABCB1 substrate cisplatin. Noteworthy, Icory selectively reversed ABCB1-overexpressing MDR cancer cells but not ABCC1- or ABCG2-mediated MDR. Further mechanistic study revealed that Icory increased the intracellular accumulation of doxorubicin in ABCB1-overexpressing cells by blocking the efflux function of ABCB1. Instead of inhibiting ABCB1 expression and localization, Icory acts as a substrate of the ABCB1 transporter by competitively binding to substrate binding sites. Collectively, these results indicated that Icory reversed ABCB1-mediated MDR by suppressing its efflux function, and it would be beneficial to increase the efficacy of these types of uncaria alkaloids and develop them to be selective ABCB1-mediated MDR-reversal agents.
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July-2017
Volume 51 Issue 1

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

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Spandidos Publications style
Huang B, Zeng Y, Li Y, Huang X, Hu N, Yao N, Chen M, Yang Z, Chen Z, Zhang D, Zhang D, et al: Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance. Int J Oncol 51: 257-268, 2017.
APA
Huang, B., Zeng, Y., Li, Y., Huang, X., Hu, N., Yao, N. ... Zeng, C. (2017). Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance. International Journal of Oncology, 51, 257-268. https://doi.org/10.3892/ijo.2017.4005
MLA
Huang, B., Zeng, Y., Li, Y., Huang, X., Hu, N., Yao, N., Chen, M., Yang, Z., Chen, Z., Zhang, D., Zeng, C."Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance". International Journal of Oncology 51.1 (2017): 257-268.
Chicago
Huang, B., Zeng, Y., Li, Y., Huang, X., Hu, N., Yao, N., Chen, M., Yang, Z., Chen, Z., Zhang, D., Zeng, C."Uncaria alkaloids reverse ABCB1-mediated cancer multidrug resistance". International Journal of Oncology 51, no. 1 (2017): 257-268. https://doi.org/10.3892/ijo.2017.4005