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Molecules 2013, 18(12), 14935-14947; doi:10.3390/molecules181214935
Article

Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells

1,†
,
2,†
,
2,†
,
3,4
 and
3,4,*
1 Department of Science and Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, China 2 Department of Oncology, Center Hospital of Nanyang, Nanyang, Henan 473000, China 3 Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, China 4 Institute of Traditional Chinese Medicine in Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, China These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 4 November 2013 / Revised: 27 November 2013 / Accepted: 27 November 2013 / Published: 4 December 2013
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Abstract

Hepatocarcinogenesis is associated with epigenetic changes, including histone deacetylases (HDACs). Epigenetic modulation by HDAC inhibition is a potentially valuable approach for hepatocellular carcinoma treatment. In present study, we evaluated the anticancer effects of sodium valproate (SVP), a known HDAC inhibitor, in human hepatocarcinoma cells. The results showed SVP inhibited the proliferation of Bel-7402 cells in a dose-dependent manner. Low dose SVP treatment caused a large and flat morphology change, positive SA-β-gal staining, and G0/G1 phase cell cycle arrest in human hepatocarcinoma cells. Low dose SVP treatment also increased acetylation of histone H3 and H4 on p21 promoter, accompanied by up-regulation of p21 and down-regulation of RB phosphorylation. These observations suggested that a low dose of SVP could induce cell senescence in hepatocarcinoma cells, which might correlate with hyperacetylation of histone H3 and H4, up-regulation of p21, and inhibition of RB phosphorylation. Since the effective concentration inducing cell senescence in hepatocarcinoma cells is clinically available, whether a clinical dose of SVP could induce cell senescence in clinical hepatocarcinoma is worthy of further study.
Keywords: hepatocarcinoma; valproic acid sodium salt; cell senescence hepatocarcinoma; valproic acid sodium salt; cell senescence
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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An, H.-M.; Xue, Y.-F.; Shen, Y.-L.; Du, Q.; Hu, B. Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells. Molecules 2013, 18, 14935-14947.

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