Neoalbaconol induces cell death through necroptosis by regulating RIPK-dependent autocrine TNFα and ROS production

摘要: Necroptosis/regulated necrosis is a caspase-independent, but receptor interacting protein kinase (RIPK)-dependent form of cell death. In previous studies, neoalbaconol (NA), constituent extracted from Albatrellus confluens, was demonstrated to induce necroptosis in some cancer lines. The molecular mechanism NA-induced described this research study. We determined that death partly dependent on tumor factor α (TNFα) feed-forward signaling. More importantly, NA abolished the ubiquitination RIPK1 by down-regulating E3 ubiquitin ligases, cellular inhibitors apoptosis 1/2 (cIAP1/2) and TNFα receptor-associated factors (TRAFs). suppression induced activation non-canonical nuclear factor-κB (NF-κB) pathway stimulated transcription TNFα. Moreover, we also found caused RIPK3-mediated reactive oxygen species (ROS) production contribution Taken together, these results suggested two distinct mechanisms are involved include RIPK1/NF-κB-dependent expression RIPK3-dependent generation ROS.