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Hsp90 inhibitor induces KG-1a cell differentiation and apoptosis via Akt/NF-κB signaling

  • Authors:
    • Jin-Hong Qin
    • Kun Wang
    • Xin-Lu Fu
    • Peng-Jun Zhou
    • Zhong Liu
    • Dan-Dan Xu
    • Yi-Fei Wang
    • De-Po Yang
    • Qiu-Ling Xie
    • Qiu-Ying Liu

  • View Affiliations

  • Published online on: July 7, 2017     https://doi.org/10.3892/or.2017.5797
  • Pages: 1517-1524
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Abstract

Heat-shock protein 90 (Hsp 90) acts as a molecular chaperone that maintains protein stability and regulates cell proliferation, survival, differentiation and apoptosis. The present study investigated the effect of Hsp90 inhibition on human acute myeloid leukemia (AML) cells using the novel small-molecule inhibitor SNX-2112. We found that SNX-2112 more potently inhibited KG-1a cell growth than the classical Hsp90 inhibitor 17-(2-dimethylaminoethyl)amino‑17-demethoxygeldanamycin as determined by CCK-8 assay. Flow cytometry was used to examine the cell cycle, differentiation, and apoptosis, and western blotting and qRT-PCR were used to analyze the underlying mechanism. The results revealed that low concentrations of SNX-2112 arrested the cells in the G2/M phase and induced their differentiation and apoptosis, possibly by suppressing Akt and inhibitor of κB kinase, a component of the nuclear factor (NF)-κB signaling pathway. We also found that SNX-2112 increased the expression of the differentiation transcription factors PU.1 and CCAAT‑enhancer-binding protein-α. Thus, SNX-2112 induced KG-1a cell differentiation, cell cycle arrest and apoptosis via modulation of Akt and NF-κB signaling, suggesting that it is a promising therapeutic agent for the treatment of AML.
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September-2017
Volume 38 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 3.8
  • Ranked Oncology
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  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Qin J, Wang K, Fu X, Zhou P, Liu Z, Xu D, Wang Y, Yang D, Xie Q, Liu Q, Liu Q, et al: Hsp90 inhibitor induces KG-1a cell differentiation and apoptosis via Akt/NF-κB signaling. Oncol Rep 38: 1517-1524, 2017.
APA
Qin, J., Wang, K., Fu, X., Zhou, P., Liu, Z., Xu, D. ... Liu, Q. (2017). Hsp90 inhibitor induces KG-1a cell differentiation and apoptosis via Akt/NF-κB signaling. Oncology Reports, 38, 1517-1524. https://doi.org/10.3892/or.2017.5797
MLA
Qin, J., Wang, K., Fu, X., Zhou, P., Liu, Z., Xu, D., Wang, Y., Yang, D., Xie, Q., Liu, Q."Hsp90 inhibitor induces KG-1a cell differentiation and apoptosis via Akt/NF-κB signaling". Oncology Reports 38.3 (2017): 1517-1524.
Chicago
Qin, J., Wang, K., Fu, X., Zhou, P., Liu, Z., Xu, D., Wang, Y., Yang, D., Xie, Q., Liu, Q."Hsp90 inhibitor induces KG-1a cell differentiation and apoptosis via Akt/NF-κB signaling". Oncology Reports 38, no. 3 (2017): 1517-1524. https://doi.org/10.3892/or.2017.5797