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In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death. When human colon cancer HCT116, CX\u20101, and LS174T cells were treated with ferroptotic agents such as sorafenib (SRF), erastin, and artesunate, data from immunoblot assay showed that ferroptotic agents induced endoplasmic reticulum (ER) stress and the ER stress response\u2010mediated expression of death receptor 5 (DR5), but not death receptor 4. An increase in the level of DR5, which is activated by binding to tumor necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL) and initiates apoptosis, was probably responsible for synergistic apoptosis when cells were treated with ferroptotic agent in combination with TRAIL. This collateral effect was suppressed in C\/EBP (CCAAT\u2010enhancer\u2010binding protein)\u2010homologous protein (CHOP)\u2010deficient mouse embryonic fibroblasts or DR5 knockdown HCT116 cells, but not in p53\u2010deficient HCT116 cells. The results from in vitro studies suggest the involvement of the p53\u2010independent CHOP\/DR5 axis in the synergistic apoptosis during the combinatorial treatment of ferroptotic agent and TRAIL. The synergistic apoptosis and regression of tumor growth were also observed in xenograft tumors when SRF and TRAIL were administered to tumor\u2010bearing mice.<\/jats:p>","DOI":"10.1002\/jcb.27456","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T15:11:27Z","timestamp":1535641887000},"page":"928-939","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Ferroptosis\u2010inducing agents enhance TRAIL\u2010induced apoptosis through upregulation of death receptor 5"],"prefix":"10.1002","volume":"120","author":[{"given":"Young\u2010Sun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Surgery School of Medicine, University of Pittsburgh Pittsburgh Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dae\u2010Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Oncology Korea University Guro Hospital Seoul 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