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

Li,Fengshan; Wang,Tiegong; Wang,Zhenyong; Chen,Xiongfei; Liu,Ruhai

doi:10.3892/mmr.2017.7355

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
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Affiliations: First Department of General Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
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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