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Article

Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction

  • Authors:
    • Wenjuan Liu
    • Yonghao Qi
    • Lingyu Liu
    • Yu Tang
    • Jing Wei
    • Lijun Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P.R. China
  • Pages: 2171-2179
    |
    Published online on: July 11, 2016
       https://doi.org/10.3892/mmr.2016.5492
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Abstract

Protein kinase B (AKT), is a pivotal component of pathways associated with cell survival, metabolism, invasion and metastasis. AKT mediates anti‑apoptotic and proliferative signaling in response to essential cytokines. Tumor necrosis factor receptor‑associated factor (TRAF)6, an E3 ubiquitin ligase, has been shown to ubiquitylate, as well as activate AKT. The present study used computational methods to determine the relevant amino acid residues at the binding site of TRAF6 and selected small molecules, which may bind to TRAF6. An ex vivo assay was performed to determine their antitumor activities and the possible mechanism of action. Quinine, a natural alkaloid that is well‑known for its therapeutic treatment of malaria, exhibited a distinct antiproliferative and pro‑apoptotic effect in HeLa and A549 tumor cell lines via the inhibition of the antiapoptotic protein, B‑cell lymphoma (BCL)‑2, and activation of the pro‑apoptotic factor, BCL‑2‑associated X protein. Quinine inhibited the lipopolysaccharide (LPS)‑induced activation of AKT by inhibiting its phosphorylation at Thr‑308 and Ser‑473, and reversing LPS‑induced proliferation. These results suggested that the inhibition of AKT activation via targeting of TRAF6 with quinine may be a viable anticancer therapeutic approach and a successful example of the alternative use of the original therapeutic properties of this well‑known natural product.
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Copy and paste a formatted citation
Spandidos Publications style
Liu W, Qi Y, Liu L, Tang Y, Wei J and Zhou L: Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction. Mol Med Rep 14: 2171-2179, 2016.
APA
Liu, W., Qi, Y., Liu, L., Tang, Y., Wei, J., & Zhou, L. (2016). Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction. Molecular Medicine Reports, 14, 2171-2179. https://doi.org/10.3892/mmr.2016.5492
MLA
Liu, W., Qi, Y., Liu, L., Tang, Y., Wei, J., Zhou, L."Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction". Molecular Medicine Reports 14.3 (2016): 2171-2179.
Chicago
Liu, W., Qi, Y., Liu, L., Tang, Y., Wei, J., Zhou, L."Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction". Molecular Medicine Reports 14, no. 3 (2016): 2171-2179. https://doi.org/10.3892/mmr.2016.5492
Copy and paste a formatted citation
x
Spandidos Publications style
Liu W, Qi Y, Liu L, Tang Y, Wei J and Zhou L: Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction. Mol Med Rep 14: 2171-2179, 2016.
APA
Liu, W., Qi, Y., Liu, L., Tang, Y., Wei, J., & Zhou, L. (2016). Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction. Molecular Medicine Reports, 14, 2171-2179. https://doi.org/10.3892/mmr.2016.5492
MLA
Liu, W., Qi, Y., Liu, L., Tang, Y., Wei, J., Zhou, L."Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction". Molecular Medicine Reports 14.3 (2016): 2171-2179.
Chicago
Liu, W., Qi, Y., Liu, L., Tang, Y., Wei, J., Zhou, L."Suppression of tumor cell proliferation by quinine via the inhibition of the tumor necrosis factor receptor‑associated factor 6‑AKT interaction". Molecular Medicine Reports 14, no. 3 (2016): 2171-2179. https://doi.org/10.3892/mmr.2016.5492
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