Inhibition of PERK-dependent pro-adaptive signaling pathway as a promising approach for cancer treatment

Abstract

In the study, we utilized commercially available cell lines of human colorectal adenocarcinoma HT-29 and human neuroblastoma SH-SY5Y. Cells were exposed to the tested PERK-dependent signaling inhibitor GSK2606414 in suitable culture media with addition of thapsigargin (500 nM) to induce ER stress. To identify the protein, Western blot with specific antibodies was used. Detection of immune complexes was performed using chemiluminescence. We found a complete inhibition of p-eIF2α expression due to the GSK2606414 inhibitor in both cell lines, SH-SY5Y and HT-29. Currently available cancer treatments are insufficient and cause various side effects. It has been assumed that utilization of small-molecule inhibitors of the PERK-dependent signaling pathway, like GSK2606414, may switch the pro-adaptive branch of UPR to its pro-apoptotic branch. It is believed that the tested inhibitor GSK2606414 may become a promising treatment for many cancer types.