Valproic acid inhibits prostate cancer cell migration by up-regulating E-cadherin expression

E-Cadherin plays important roles in cell-cell adhesion, epithelial-to-mesenchymal transition, cancer cell migration and invasion. Valproic acid (VPA), a well-known inhibitor of class I and class II histone deacetylases, has been considered a promising anticancer drug due to its capacity of inducing cancer cell proliferation arrest and death through different mechanisms. However, effects of VPA on E-cadherin mediated cell-cell adhesion and cancer cell migration remain unclear. In the present study, we found that VPA potently induced hyperacetylation of histone H3 and H4, increased the expression of E-cadherin and inhibited cell migration in prostate cancer cells. Furthermore, knock-down of E-cadherin significantly restored the effects of VPA on cell migration, while over-expression of E-cadherin in prostate cancer cells significantly inhibited cell migration to a similar level as VPA treatment. These results thus suggest that up-regulation of E-cadherin and inhibition of cell migration may represent a new anticancer mechanism of VPA.