TY - JOUR T1 - Role of Death Receptors-associated Lipid Rafts in Oxaliplatin-induced Death Mode Regulation of HepG2 Cells JF - Anticancer Research JO - Anticancer Res SP - 2573 LP - 2582 DO - 10.21873/anticanres.14228 VL - 40 IS - 5 AU - SUNG-CHUL LIM AU - KESHAB RAJ PARAJULI AU - SONG IY HAN Y1 - 2020/05/01 UR - http://ar.iiarjournals.org/content/40/5/2573.abstract N2 - Background/Aim: We previously showed that oxaliplatin induces necrotic-like cell death in hepatocarcinomas, and combination with ursodexoycholic acid (UDCA) significantly shifts the necrotic-like death to apoptosis. Since cell death mode is crucial on inflammatory responses and chemotherapeutic efficacy, the mechanism underlying determination of cell death mode by UDCA was investigated in this study. Materials and Methods: Apoptosis or necrosis was determined by apoptotic body formation, caspase-8 activity, LDH release and PI inclusion. The involvement of lipid rafts and death receptors was examined by rafts fractionation, confocal microscopy and gene silencing assays. Results: UDCA combination enhanced recruitment of death receptors and adaptors into cholesterol-enriched lipid rafts, and induced a stronger raft clustering. Lipid raft disruption decreased the UDCA/oxaliplatin-mediated apoptosis and increased necrotic-like death. Conclusion: UDCA promotes lipid raft localization of multiple death receptors, thereby contributing to a shift of cell death mode from oxaliplatin-induced necrotic death to apoptosis in HepG2 cells. ER -