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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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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