Repositioning of amprenavir as a novel extracellular signal-regulated kinase-2 inhibitor and apoptosis inducer in MCF-7 human breast cancer

  • Authors:
    • Wenchun Jiang
    • Xin Li
    • Tongyu Li
    • Hailian Wang
    • Wei Shi
    • Ping Qi
    • Chunyang Li
    • Jie Chen
    • Jinku Bao
    • Guodong Huang
    • Yi Wang
  • View Affiliations

  • Published online on: January 24, 2017     https://doi.org/10.3892/ijo.2017.3860
  • Pages: 823-834
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Abstract

Computational drug repositioning by virtually screening existing drugs for additional therapeutic usage could efficiently accelerate anticancer drug discovery. Herein, a library of 1447 Food and Drug Administration (FDA)-approved small molecule drugs was screened in silico for inhibitors of extracellular signal-regulated kinase 2 (ERK2). Then, in vitro kinase assay demonstrated amprenavir, a HIV-1 protease inhibitor, as a potential kinase inhibitor of ERK2. The in vivo kinase assay indicated that amprenavir could inhibit ERK2-mediated phosphorylation of BimEL at Ser69. Amprenavir could suppress this phosphorylation in MCF-7 cells, which may further facilitate the association of BimEL with several pro-survival molecules. Additionally, inhibition of ERK2-BimEL signaling pathway by amprenavir could contribute to its anti-proliferative and apoptosis-inducing activity in MCF-7 cells. Finally, in vivo tumor growth and immunohistochemical studies confirmed that amprenavir remarkably suppressed tumor proliferation and induce apoptosis in MCF-7 xenografts. Taken together, amprenavir can effectively inhibit the kinase activity of ERK2, and thus induces apoptosis and inhibits tumor growth in human MCF-7 cancer cells both in vitro and in vivo, making amprenavir a promising candidate for future anticancer therapeutics.
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March-2017
Volume 50 Issue 3

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

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Spandidos Publications style
Jiang W, Li X, Li T, Wang H, Shi W, Qi P, Li C, Chen J, Bao J, Huang G, Huang G, et al: Repositioning of amprenavir as a novel extracellular signal-regulated kinase-2 inhibitor and apoptosis inducer in MCF-7 human breast cancer. Int J Oncol 50: 823-834, 2017
APA
Jiang, W., Li, X., Li, T., Wang, H., Shi, W., Qi, P. ... Wang, Y. (2017). Repositioning of amprenavir as a novel extracellular signal-regulated kinase-2 inhibitor and apoptosis inducer in MCF-7 human breast cancer. International Journal of Oncology, 50, 823-834. https://doi.org/10.3892/ijo.2017.3860
MLA
Jiang, W., Li, X., Li, T., Wang, H., Shi, W., Qi, P., Li, C., Chen, J., Bao, J., Huang, G., Wang, Y."Repositioning of amprenavir as a novel extracellular signal-regulated kinase-2 inhibitor and apoptosis inducer in MCF-7 human breast cancer". International Journal of Oncology 50.3 (2017): 823-834.
Chicago
Jiang, W., Li, X., Li, T., Wang, H., Shi, W., Qi, P., Li, C., Chen, J., Bao, J., Huang, G., Wang, Y."Repositioning of amprenavir as a novel extracellular signal-regulated kinase-2 inhibitor and apoptosis inducer in MCF-7 human breast cancer". International Journal of Oncology 50, no. 3 (2017): 823-834. https://doi.org/10.3892/ijo.2017.3860