IMB-6G induces endoplasmic reticulum stress-mediated apoptosis in human nasopharyngeal carcinoma cells.

IMB-6G is a novel N-substituted sophoridine acid that has been reported to have anticancer effects. The purpose of the present study was to investigate the effect and underlying mechanism of IMB-6G on human nasopharyngeal carcinoma (NPC) cells. The NPC cell line C666-1 was used in the present study and treated with different concentrations of IMB-6G (0, 1, 2 and 5 mu M) for 24 h. Subsequently, cell viability was determined using the Cell Counting kit-8 assay and cell apoptosis was analyzed by performing flow cytometry. The expression levels of genes and proteins in the current study were determined using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Results indicated that IMB-6G dose-dependently inhibited C666-1 cell viability and induced apoptosis. It was also revealed that IMB-6G induced apoptosis via inducing endoplasmic reticulum (ER) stress activation. Notably, IMB-6G administration enhanced the expression levels of Binding immunoglobulin protein and CCAAT-enhancer-binding protein homologous protein in C666-1 cells. Further analysis suggested that IMB-6G treatment activated inositol-requiring enzyme 1 alpha (IRE1 alpha) and PKR-like ER kinase (PERK) signaling pathways in C666-1 cells. In addition, silencing of IRE1 alpha and PERK significantly reversed IMB-6G-induced cell growth inhibition and apoptosis. In conclusion, the present findings indicated that IMB-6G induced ER stress-mediated apoptosis through activating IRE1 alpha and PERK signaling pathways. The present study suggests that IMB-6G may be a promising agent for NPC treatment.