Comparison of Anticancer Effects of Carbamazepine and Valproic Acid

Iran Red Crescent Med J. 2016 Aug 4;18(10):e37230. doi: 10.5812/ircmj.37230. eCollection 2016 Oct.

Abstract

Background: Valproic acid (VPA) and carbamazepine (CBZ), two widely used antiepileptic drugs, have recently been found to inhibit histone deacetylases (HDAC). HDAC inhibitors (HDACIs) have various effects on cancer cells.

Objectives: The aim of this study was to compare the anticancer activity of these drugs on SW480 colon cancer cell lines.

Methods: In the present experimental study, implemented during 2014 - 2015 in Iran, after incubation of cells into 96-well plates with 5,500 cells/well, the tested drugs were added, and cytotoxic effects were assessed by MTT. Moreover, after incubation of 8×106 cells in 75 cm² flasks to obtain β-catenin levels and 106 cells in a six-well plate to obtain vascular endothelial growth factor (VEGF) levels , these levels were estimated using enzyme-linked immunosorbent assay (ELISA) analysis.

Results: Through MTT assay, we found that the inhibitory concentration of 50% (IC50) values for VPA and CBZ were 2.5 mM and 5 μM, respectively in comparison to controls in terms of total concentration and times evaluated (P < 0.0001). We also found that treatments with these drugs decreased levels of β-catenin (P < 0.0001) and VEGF (P < 0.0001) significantly more than controls.

Conclusions: VPA and CBZ treatments caused a decrease in β-Catenin and VEGF levels in SW480 colon cancer cell lines. These results suggest that CBZ can be considered a potential antitumor drug with potencies different from VPA.

Keywords: Histone Deacetylase Inhibitor; VEGF; β-Catenin.