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Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells

2013; Multidisciplinary Digital Publishing Institute; Volume: 18; Issue: 12 Linguagem: Inglês

10.3390/molecules181214935

1433-1373

Hong‐Mei An, Yongfei Xue, Yanli Shen, Qin Du, Bing Hu,

Protein Degradation and Inhibitors

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.