Histone deacetylase inhibitor quisinostat activates caspase signaling and upregulates p53 acetylation to inhibit the proliferation of HepG2 cells

  • Authors:
    • Fengshan Li
    • Tiegong Wang
    • Zhenyong Wang
    • Xiongfei Chen
    • Ruhai Liu
  • View Affiliations

  • Published online on: August 24, 2017     https://doi.org/10.3892/mmr.2017.7355
  • Pages: 6094-6101
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Abstract

Histone deacetylase inhibitor (HDACi) has been a major target of anticancer agents. Quisinostat (JNJ‑26481585), a novel second‑generation HDACi, has previously demonstrated antiproliferative activity against non‑small cell lung cancer; however, the function of quisinostat in hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, it was revealed that quisinostat suppressed the cell viability of HepG2 cells in vitro and in vivo. Increased cell apoptosis was observed in quisinostat‑treated HepG2 cells. The underlying mechanism revealed that quisinostat treatment activates the cleavage of caspase proteins. Furthermore, quisinostat upregulated p53 acetylation at K381/K382 sites by impairing the interaction between histone deacetylase 6 and p53, which resulted in the activation of p53, and triggered cell cycle arrest at the G1 phase. Collectively, the results of the present study demonstrated the antiproliferative effect of quisinostat on HepG2 cells; these results suggest that histone deacetylase may be a promising therapeutic target of HCC.
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November-2017
Volume 16 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li F, Wang T, Wang Z, Chen X and Liu R: Histone deacetylase inhibitor quisinostat activates caspase signaling and upregulates p53 acetylation to inhibit the proliferation of HepG2 cells. Mol Med Rep 16: 6094-6101, 2017.
APA
Li, F., Wang, T., Wang, Z., Chen, X., & Liu, R. (2017). Histone deacetylase inhibitor quisinostat activates caspase signaling and upregulates p53 acetylation to inhibit the proliferation of HepG2 cells. Molecular Medicine Reports, 16, 6094-6101. https://doi.org/10.3892/mmr.2017.7355
MLA
Li, F., Wang, T., Wang, Z., Chen, X., Liu, R."Histone deacetylase inhibitor quisinostat activates caspase signaling and upregulates p53 acetylation to inhibit the proliferation of HepG2 cells". Molecular Medicine Reports 16.5 (2017): 6094-6101.
Chicago
Li, F., Wang, T., Wang, Z., Chen, X., Liu, R."Histone deacetylase inhibitor quisinostat activates caspase signaling and upregulates p53 acetylation to inhibit the proliferation of HepG2 cells". Molecular Medicine Reports 16, no. 5 (2017): 6094-6101. https://doi.org/10.3892/mmr.2017.7355