IPS-1 plays a dual function to directly induce apoptosis in murine melanoma cells by inactivated Sendai virus

Inactivated Sendai virus (HVJ-E) directly kills cancer cells by inducing apoptosis through a mechanism mediated by Janus kinases/signal transducers and activators of transcription (JAK/STAT) signaling pathways. However, whether other signaling pathways are involved remain largely unknown. This study aimed to investigate the mechanism underlying HVJ-E-induced apoptosis in murine B16F10 melanoma cells. We found that HVJ-E induced B16F10 cell apoptosis via the caspase pathway, particularly caspase-9, which mediates the intrinsic apoptotic pathway. Mitogen-activated protein kinase (MAPK) pathway activation also contributed to HVJ-E-induced apoptosis. Whereas caspase pathway involvement depended on both IFN- promoter stimulator-1 (IPS-1) and type I interferon (IFN), MAPK pathway activation was independent of type I IFN but involved IPS-1. In addition, intratumoral HVJ-E treatment displayed a direct oncolytic effect in an in vivo BALB/c nude mouse melanoma model. Collectively, our data provides new insights into the mechanism underlying HVJ-E-induced apoptosis in tumor cells. What's new? Inactivated Sendai virus (HVJ-E) can directly kill human cancer cells via apoptosis, but the molecular mechanisms aren't fully understood. In this study in a murine melanoma cell line, the authors found that the caspase and MAPK pathways are involved, and that IPS-1 (IFN- promoter stimulator-1) plays a dual function. In addition, when tumors in live mice were directly injected with the inactivated virus, growth of the tumors was inhibited. These results offer new insights into the selective killing of cancer cells by oncolytic viruses, and suggest new therapeutic targets for inducing apoptosis in cancer cells.