title: Valproic acid inhibits prostate cancer cell migration by up-regulating E-cadherin expression.
abstract: 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.
authors: Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Shanghai, People's Republic of China.
authors: Lei
authors: L
authors: Zhang
authors: Guiying
authors: G
authors: Wang
authors: Lin
authors: L
authors: Wang
authors: Chenlin
authors: C
authors: Song
authors: Xinhua
authors: X
authors: Wang
authors: Jiuhong
authors: J
authors: Kang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids / Q000235:genetics; D011471:Prostatic Neoplasms / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects*; D014635:Valproic Acid / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D015820:Cadherins; D056572:Histone Deacetylase Inhibitors; D014635:Valproic Acid