RIP1 and RIP3 contribute to shikonin-induced DNA double-strand breaks in glioma cells via increase of intracellular reactive oxygen species

摘要: Shikonin has been reported to induce glioma cell death via necroptosis, a type of programmed necrosis primarily mediated by RIP1 and RIP3. Although RIP3 are found regulate some features such as energy depletion cellular membrane disruption, it remains unclear whether could modulate DNA double strand breaks (DSBs), which is crucial event leading chromatinolysis. In this study, we used lines mice model xenograft investigate the roles in shikonin-induced DSBs. We that shikonin induced upregulation RIP3, necrosome formation DSBs vitro vivo. investigation showed reduction viabilities were both prevented when or was pharmacologically inhibited specific inhibitor genetically knocked down with siRNA. Then, proved suppression intracellular ROS antioxidant NAC caused either hydrogen peroxide shikonin, suggesting played role regulation cells shikonin. Further, regulated overproduction causing excessive generation mitochondrial superoxide GSH, indicating downstream signal Taken together, demonstrated contributed increase levels.