Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells

Molecules

Hong-Mei An¹  Yong-Fei Xue³  Yan-Li Shen³  Qin Du² 

[1] Department of Science and Technology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, China; E-Mail:;Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 202032, China; E-Mail:;Department of Oncology, Center Hospital of Nanyang, Nanyang, Henan 473000, China; E-Mails:

关键词: hepatocarcinoma;    valproic acid sodium salt;    cell senescence;   

DOI  :  10.3390/molecules181214935

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.