5-ALA-PDT induces RIP3-dependent necrosis in glioblastoma

摘要: Glioblastoma constitute the most frequent and deadliest brain tumors of astrocytic origin. They are resistant to all current therapies associated with a high rate recurrence. were previously shown respond treatments by 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) mainly activating necrotic type cell death. The receptor-interacting protein 3 (RIP3) has recently been outlined as key mediator this caspase-independent form programmed In present study, we analyzed mechanism induced 5-ALA-PDT in human glioblastoma cells explored role RIP3 context. Our results show that PDT-induced necrosis is dependent on RIP3, which forms aggregates colocalizes RIP1 following photosensitization. We demonstrate PDT-mediated singlet oxygen production cause RIP3-dependent pathway activation. also prove PDT induces formation pro-necrotic complex containing but lacking caspase-8 FADD, two proteins usually part necrosome when TNF-α used stimulus. Thus, hypothesize might lead different whose components, besides still unknown. cases, characterized constitutive activation NF-κB. This factor regulator various processes, such inflammation, immune response, growth or apoptosis. Its inhibition was further sensitize necrosis, however, no difference upshift aggregation could be observed NF-κB inhibited.