Valproic Acid sodium

Valproic acid acts through a distinct pathway that involves direct inhibition of histone deacetylase (IC(50) for HDAC1 = 0.4 mM). Valproic acid mimics the histone deacetylase inhibitor trichostatin A, causing hyperacetylation of histones in cultured cells. Valproic acid, like trichostatin A, also activates transcription from diverse exogenous and endogenous promoters. Valproic acid and trichostatin A have remarkably similar teratogenic effects in vertebrate embryos, while non-teratogenic analogues of valproic acid do not inhibit histone deacetylase and do not activate transcription. ^[1]

Valproic acid induces proliferation of peroxisomes in the rodent liver. Valproic acid at a concentration of 1 mM induces relief of this repression by Gal4 fusions of N‐CoR, TR or PPARδ in a cell line expressing the ligand‐binding domain of PPARδ fused to the DNA‐binding domain of the glucocorticoid receptor (GR) together with a GR‐controlled reporter gene. Valproic acid induces accumulation of hyperacetylated histone and inhibits HDAC activity. Valproic acid induces a specific type of differentiation characterized by reduced proliferation, morphological alterations, marker gene expression and particularly the accumulation of the AP-2 transcription factor as a potential marker of neuronal or neural crest cell-like differentiation in F9 teratocarcinoma cells. Valproic acid impairs cell proliferation or survival as indicated by decreased incorporation of [³H]thymidine in F9 and P19 teratocarcinoma cells. ^[2]

Valproic acid delays growth of the primary tumors in the MT‐450 rat breast cancer model. ^[2]

• Cell lines

  HeLa cells

• Concentrations

  IC50 of 0.54, 2.8, and 2.4 mM for HDAC2, HDAC5, and HDAC6, respectively.

• Incubation Time

  12 h

• Method

  Cells were treated with various concentrations of drug for 12 h.

• Animal Models

  MT-450 rat breast cancer model

• Dosages

  1.25 mM/kg

• Administration

  i.p.