Ferroptosis-inducing agents enhance TRAIL-induced apoptosis through upregulation of death receptor 5

Autor: Dae Hee Lee, Jian Yu, David L. Bartlett, Yong Seok Park, Haroon A. Choudry, Yong J. Lee, Seong Hye Park, So Yeon Jeong, Young Sun Lee, Sang Cheul Oh
Rok vydání: 2018
Předmět:
0301 basic medicine
Programmed cell death
Artesunate
Mice
Nude
Apoptosis
CHOP
Biochemistry
Piperazines
Article
TNF-Related Apoptosis-Inducing Ligand
03 medical and health sciences
Mice
0302 clinical medicine
Downregulation and upregulation
Proto-Oncogene Proteins
Animals
Ferroptosis
Humans
Receptor
Molecular Biology
Mice
Inbred BALB C
Chemistry
Endoplasmic reticulum
Drug Synergism
Cell Biology
Sorafenib
Endoplasmic Reticulum Stress
HCT116 Cells
Xenograft Model Antitumor Assays
Tumor Burden
Up-Regulation
Receptors
TNF-Related Apoptosis-Inducing Ligand
030104 developmental biology
030220 oncology & carcinogenesis
Gene Knockdown Techniques
Colonic Neoplasms
Cancer research
Unfolded protein response
Tumor necrosis factor alpha
Female
Tumor Suppressor Protein p53
Apoptosis Regulatory Proteins
Transcription Factor CHOP
Zdroj: Journal of cellular biochemistry. 120(1)
ISSN: 1097-4644
Popis: Ferroptosis is considered genetically and biochemically distinct from other forms of cell death. In this study, we examined whether ferroptosis shares cell death pathways with other types of cell death. When human colon cancer HCT116, CX-1, and LS174T cells were treated with ferroptotic agents such as sorafenib (SRF), erastin (ERA), and artesunate (ART), data from immunoblot assay showed that ferroptotic agents induced endoplasmic reticulum (ER) stress and the ER stress response-mediated expression of death receptor 5 (DR5), but not death receptor 4 (DR4). An increase in the level of DR5, which is activated by binding to tumor necrosis factor-related apoptosis-inducing 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-enhancer-binding protein)-homologous protein (CHOP)-deficient mouse embryonic fibroblasts or DR5 knockdown HCT116 cells, but not in p53-deficient HCT116 cells. The results from in vitro studies suggest the involvement of the p53-independent 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-bearing mice.
Databáze: OpenAIRE
Externí odkaz: