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Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells
AbstractHepatocarcinogenesis 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.
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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.View more citation formats
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(12):14935-14947.Chicago/Turabian Style
An, Hong-Mei; Xue, Yong-Fei; Shen, Yan-Li; Du, Qin; Hu, Bing. 2013. "Sodium Valproate Induces Cell Senescence in Human Hepatocarcinoma Cells." Molecules 18, no. 12: 14935-14947.