Nanoencapsulation of Cordycepin Induces Switching from Necroptosis to Apoptosis in Human Oral Cancer Cells (HSC-4) Through Inhibition of Receptor-Interacting Serine/Threonine-Protein Kinase 3 (RIPK3) and Autophagy Modulation

Human oral squamous carcinoma is considered the most common cancer; it imposes multiple and dental consequences as a result of cancer treatment. We previously found that nanoencapsulation cordycepin (CS) could inhibit cells. However, mechanism action was not understood. The aim this study to investigate signaling pathway by which CS encapsulated nanoparticles (NPs) activate inhibition cell growth. demonstrated human (HSC-4) cells underwent necroptosis when incubated with high concentrations CS, but either low or NPs. High CS-induced HSC-4 cells, reduction in apoptotic ( BAX, Caspase-3, Caspase-8, Caspase-9) autophagic genes LC3, Atg5, Atg12). significantly induced expression gene LC3. Interestingly, NPs significant increase P53, Caspase-9), decrease P62, Atg12) necroptotic receptor-interacting serine/threonine-protein kinase 3 [RIPK3]) . also enhanced accumulation cellular protein decreased secreted supernatant levels. Moreover, had higher efficacy terms reactive oxygen species (ROS) generation-mediated autophagy compared nonencapsulated suggesting can switch program death from apoptosis. In conclusion, have defense strategy against apoptosis, problem be solved through use encapsulation combined nanotechnology.