The cytotoxic activity evaluation of an arylhydrazone derivative of mefenamic acid on HEPG2 liver cancer cells and normal gingival HGF cells

Abstract

Background and objectiveAlthough the anti-cancer effects of nonsteroidal anti-inflammatory drugs have been shown in many studies, the results are still controversial. This study aimed to investigate the effects of an arylhydrazone derivative of Mefenamic acid (AHD) on HepG2 liver cancer cells and human gingival fibroblasts (HGFs). MethodsThe cell lines were divided into a control group and groups exposed to 1, 10, 20, 50, and 100 μg/ml concentrations of Mefenamic acid (MA) and its arylhydrazone derivative (AHD). The survival rate was measured using the MTT assay. The apoptosis and cell cycle rates were evaluated by flow cytometry at 24 and 48 h. The data were compared between groups using the one-way analysis of variance. ResultsThe results indicated that the survival rates of HEPG2 and normal cancer cells decreased significantly at 20, 50, and 100 μg/ml of MA and AHD compared to the control group at 24 (IC50 = 52.69 and IC50 = 45.39 μg/ml) and 48 h (IC50 = 27.56 μg/ml and IC50 = 23.68 μg/ml) (P < 0.0001). The significant increases of 17.04 and 17.31 times in the final apoptosis were observed in cancer cells treated with MA and AHD, respectively, when compared to control group in 48 h (P < 0.0001). A decreased G1 phase and increased S and G2 phases were found in cancer cells treated with MA and AHD in 48 h compared to control (p < 0.0001****, p < 0.001***, and p < 0.01**, respectively). ConclusionThe results of this study demonstrate that MA and AHD cause cytotoxic effects on HepG2 cancer cells through the apoptosis pathway by arresting cells in the G2 phase. MA showed a more cytotoxic effect than AHD. The cytotoxic effects were also reported in HGFs.