Valproic acid sodium salt (Sodium Valproate) inhibits the growth dose- and time-dependently with an IC50 of appr 10 and 4 mM at 24 and 72 h, respectively. Valproic acid sodium salt significantly attenuates the activities of total, cytosol and nuclear HDACs. Valproic acid sodium salt increases the form of acetylated histone 3 in HeLa cells. Valproic acid sodium salt (1-3 mM) induces a G1 phase arrest, while 10 mM Valproic acid sodium salt significantly induces a G2/M phase arrest of cell cycle in HeLa cells. In addition, Valproic acid sodium salt increases the percentage of sub-G1 cells in HeLa cells in a dose-dependent manner at 24 h.
Valproic acid sodium salt inhibits the mRNA and protein expression of VEGF, VEGFR2 and bFGF. Valproic acid sodium salt inhibits the protein expression of HDAC1, increases histone H3 acetylation, and enhances the accumulation of hyperacetylated histone H3 on VEGF promoters.
Valproic acid sodium salt treatment results in increased levels of phosphorylated AMPK/ACC in primary mouse hepatocytes. Phosphorylation of ACC following Valproic acid sodium salt treatment is AMPK-dependent. Valproic acid sodium salt inhibits the deacetylase activity of both mouse liver nuclear extracts and human recombinant HDAC1 while of the metabolites of Valproic acid, only 2-ene-Valproic acid and 4-ene-Valproic acid diminish deacetylase activity.