Effects of an aryl hydrazone derivative of naproxen on HepG2 liver cancer and HGF gingival fibroblasts cell lines

Nonsteroidal anti-inflammatory drugs are suggested to have anti-cancer effects in many studies, but elucidation of mode of action remains a challenging task. The present study was aimed to evaluate the effect of an Aryl hydrazone derivative of Naproxen (AHD) on HepG2 liver cancer cells and HGF gingival fibroblasts. The mentioned cell lines were randomly divided into control groups and test groups exposed to 1, 10, 20, 50, and 100 & mu;g/mL of Naproxen and (AHD). The cytotoxic effects of the compounds were measured using the MTT assay. The rate of apoptosis and cell cycle were also evaluated using flow cytometry at 24 and 48 h. The data were compared between groups using one-way analysis of variance. The results showed a significantly reduced viability of liver cancer cells by 20, 50, and 100 & mu;g/mL of Naproxen, and AHD after 24 h (IC50 = 51.35 & mu;g/ mL and IC50 = 87.05 & mu;g/ mL) and 48 h (IC50 = 24.92 & mu;g/ mL and IC50 = 20.82 & mu;g/ mL) (p < 0.0001). Exposure to Naproxen and AHD increased the late apoptosis rate 9.10 and 6.42 times respectively in HepG2 cancer cells compared to the control group at 48 h. (**** p < 0.0001). In the group treated with AHD, a significant decrease in G1 and a significant increase in S and G2 phases occurred in the percentage of arrested cells in HepG2 cancer at 24 h (****p < 0.0001). A significant decrease in G1 and a significant increase in S phases of Naproxen and AHD occurred in the percentage of arrested cells on HepG2 cancer at 48 h (***p < 0.001, **p < 0.01, ****p < 0.0001 ***p < 0.001 respectively). The results of this study demonstrate that Naproxen and the evaluated AHD induce cytotoxic effects in the HepG2 cancer cell line through the apoptosis pathway by cell arrest in the G2/M phase. The less cytotoxicity was observed in gingival fibroblasts than in cancer cells.