Valproic acid exerts an anti-tumor effect on tongue cancer sas cells in vitro and in vivo

Abstract

Background: Valproic acid (VPA) is a drug approved by the Food and Drug Administration for epilepsy and bipolar disorders. It is also a known histone deacetylase inhibitor and has been evaluated as an anti-cancer agent. However, the in vitro and in vivo anti-tumor effect of VPA on human tongue cancer has not been evaluated. Materials and Methods: We tested VPA for its anti-tumor activity on the human tongue cancer (SAS) cell line in vitro and in vivo in a tumor xenograft model in mice. The effect of VPA on the cell cycle and apoptosis was examined. Results: Growth inhibition was noted when SAS, squamous cell carcinoma 25 and OECM-1 cells were treated with various doses of VPA for 24-72 h, and it was found that VPA treatment caused G1 arrest and apoptosis in SAS cells. VPA also inhibited the phosphorylation of Akt and ERK in SAS cells in vitro. Tumor growth inhibition was observed in NOD/SCID mice bearing xenografts of human tongue cancer that were treated with a VPA dose of 400 mg/kg/day. Conclusions: This study demonstrates that VPA can inhibit the growth of human tongue cancer cells in vitro and in vivo without causing any significant adverse effects.

Keywords

• Valproic acid
• oral squamous cell carcinoma
• human tongue cancer
• cell cycle
• apoptosis