Dual effects of sodium butyrate on hepatocellular carcinoma cells

Sodium butyrate (NaBu), a histone deacetylase inhibitor, has been shown to inhibit cell growth, induce cell differentiation and apoptosis in multiple cell lines. In present study, we revealed the dual effects of NaBu in regulating hepatocellular carcinoma (HCC) cells. In two different HCC cell lines, SK-Hep1 and SMMC-7721, low concentrations of NaBu induced a significant increase in cell growth ratio and S-phase cell percentage, accompanied by a reduced p21 Cip1 expression at both mRNA and protein levels, while dissimilarly, high concentrations of NaBu inhibited cell growth and induced G1 arrest through up-regulation of p21 Cip1 and p27 Kip1 protein expression. The reduction of p45 Skp2 expression further indicated that the ubiquitin-mediated protein degradation might play a role in NaBu-induced up-regulation of p21 Cip1 and p27 Kip1. Moreover, the high concentration of NaBu was also able to trigger HCC cell apoptosis. Taken together, these results demonstrate the distinct effects of NaBu at different dosages. This finding may contribute to develop more effective tumor therapeutic protocols of NaBu in HCC.