Objective Isoliquiritigenin(ISL),a licorice chalconoid,is considered to be a bioactive agent with chemopreventive potential.This study investigates the mechanisms involved in ISL-induced apoptosis in human cervical carcinoma HeLa cells.Methods Cell viability was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide(MTT)assay.Apoptosis was determined by flow cytometry using an Annexin V-FITC Apoptosis Detection Kit.The intracellular ROS levels were assessed using a 2,7-dichlorofluorescein probe assay.The mitochondrial membrane potential was measured with the dual-emission potential-sensitive probe 5,5',6,6'-tetra-chloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide(JC-1).The degradation of poly-ADP-ribose polymerase(PARP)protein,the phosphorylation of PKR-like ER kinase(PERK),the phosphorylation of the α-subunit of eukaryotic initiation factor 2(eIF2α),the expression of the 78 kD glucose-regulated protein(GRP 78),and the activation of caspase-12 were analyzed via western blot analysis.Results ISL significantly inhibited the proliferation,the increase in ROS levels and apoptotic rates of HeLa cells in a concentration-dependent manner.Moreover,ISL induced mitochondrial dysfunction,caspase activation,and PARP cleavage,which displayed features of mitochondria dependent on apoptotic signals.Besides,exposure of HeLa cells to ISL triggered endoplasmic reticulum(ER)stress,as indicated by the increase in p-eIF2α and GRP78 expression,ER stress-dependent apoptosis is caused by the activation of ER-specific caspase-12.Conclusion The findings from our study suggest that ISL-induced oxidative stress causes HeLa cell apoptosis via the mitochondrion-dependent and the ER stress-triggered signaling pathways.
