Casticin elicits inflammasome-induced pyroptosis through activating PKR/JNK/NF-κB signal in 5-8F cells

Abstract

Casticin is one of the effective ingredients of fructus viticis. Most studies have shown that casticin has a strong anti-proliferation activity against various tumor cells. However, its anti-tumor effect and molecular mechanism in nasopharyngeal carcinoma remain unclear. In this study, we demonstrated that the casticin selectively inhibited the proliferation of 5-8F cells in vitro. Further analysis revealed that casticin treatment significantly increased sub-G2 phase and incited pyroptotic process. Moreover, we demonstrated that PKR participated in in regulating the process of GSDMD-dependent pyroptotic tumor cell death. PKR knockdown alleviated the activation of JNK pathway and the expression of its downstream proteins, including cleaved caspase-1, GSDMD-N, interleukin-1β. These findings indicate that PKR/JNK/NF-κB signal is essential for casticin-induced caspase-1 inflammasome formation and inflammatory cytokines release in 5-8F cell.