Effect of glycidamide on cellular stresses, apoptosis and its association with JNK signaling pathway

Background and Aim: Glycidamide (2,3-epoxypropanamide) is a white, genotoxic, and neurotoxic compound, and represents the most reactive epoxide metabolite of acrylamide formed in the liver. The aim of this study was to investigate the effects of glycidamide on the oxidative stress, the ER stress, and the apoptosis in HepG2 cells and to assess the role of the JNK signaling pathway in these processes. Materials and Methods: The effect of glycidamide alone and with 20 µM JNK inhibitor SP600125 on cell viability in HepG2 cells was evaluated by MTT assay. Then, the effect of 190 µM glycidamide alone and when applied together with SP600125 pretreatment on protein carbonyl, ATF4, JNK, procaspase-3 and active caspase-3 levels was analyzed by Western blot method. Results: Treatment of HepG2 cells with 37.5 and 190 µM glycidamide for 24 hours significantly decreased cell viability, while markedly increasing protein carbonyl, ATF4, active caspase-3 levels, and p-JNK/JNK ratio. Pretreatment with SP600125 prior to 190 µM glycidamide exposure significantly increased cell viability and ATF4 levels, while reducing protein carbonyl, active caspase-3 levels, and p-JNK/JNK ratio. Conclusion: This study demonstrates that glycidamide increases cytotoxicity, cellular stress responses and apoptosis in HepG2 cells; these effects are regulated via the JNK signaling pathway.