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Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression

Ferroptosis is a type of programmed cell death that depends on iron and is characterized by the accumulation of lipid peroxides. In the present study, we investigated the nature of the interplay between ferroptosis and other forms of cell death such as apoptosis. Human pancreatic cancer PANC-1 and B...

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Autores principales: Hong, Se Hoon, Lee, Dae-Hee, Lee, Young-Sun, Jo, Min Jee, Jeong, Yoon A, Kwon, William T., Choudry, Haroon A., Bartlett, David L., Lee, Yong J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777762/
https://www.ncbi.nlm.nih.gov/pubmed/29383150
http://dx.doi.org/10.18632/oncotarget.23046
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author Hong, Se Hoon
Lee, Dae-Hee
Lee, Young-Sun
Jo, Min Jee
Jeong, Yoon A
Kwon, William T.
Choudry, Haroon A.
Bartlett, David L.
Lee, Yong J.
author_facet Hong, Se Hoon
Lee, Dae-Hee
Lee, Young-Sun
Jo, Min Jee
Jeong, Yoon A
Kwon, William T.
Choudry, Haroon A.
Bartlett, David L.
Lee, Yong J.
author_sort Hong, Se Hoon
collection PubMed
description Ferroptosis is a type of programmed cell death that depends on iron and is characterized by the accumulation of lipid peroxides. In the present study, we investigated the nature of the interplay between ferroptosis and other forms of cell death such as apoptosis. Human pancreatic cancer PANC-1 and BxPC-3 and human colorectal cancer HCT116 cells were treated with ferroptotic agents such as erastin and artesunate (ART) in combination with the apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We observed synergistic interaction of erastin or ART with TRAIL as determined by cell death assay, caspase activation, poly [ADP-ribose] polymerase 1 (PARP-1) cleavage, flow cytometry analysis, and lipid peroxidation assay. Moreover, erastin and ART induced endoplasmic reticulum (ER) stress and promoted p53 upregulated modulator of apoptosis (PUMA) expression via C/EBP-homologous protein (CHOP). Synergy of erastin/ART and TRAIL was abolished in PUMA-deficient HCT116 cells and CHOP-deficient mouse embryonic fibroblasts, but not in p53-deficient HCT116 cells. The results suggest the involvement of the p53-independent CHOP/PUMA axis in response to ferroptosis inducers, which may play a key role in ferroptotic agent-mediated sensitization to TRAIL-induced apoptosis.
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spelling pubmed-57777622018-01-30 Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression Hong, Se Hoon Lee, Dae-Hee Lee, Young-Sun Jo, Min Jee Jeong, Yoon A Kwon, William T. Choudry, Haroon A. Bartlett, David L. Lee, Yong J. Oncotarget Research Paper Ferroptosis is a type of programmed cell death that depends on iron and is characterized by the accumulation of lipid peroxides. In the present study, we investigated the nature of the interplay between ferroptosis and other forms of cell death such as apoptosis. Human pancreatic cancer PANC-1 and BxPC-3 and human colorectal cancer HCT116 cells were treated with ferroptotic agents such as erastin and artesunate (ART) in combination with the apoptotic agent tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). We observed synergistic interaction of erastin or ART with TRAIL as determined by cell death assay, caspase activation, poly [ADP-ribose] polymerase 1 (PARP-1) cleavage, flow cytometry analysis, and lipid peroxidation assay. Moreover, erastin and ART induced endoplasmic reticulum (ER) stress and promoted p53 upregulated modulator of apoptosis (PUMA) expression via C/EBP-homologous protein (CHOP). Synergy of erastin/ART and TRAIL was abolished in PUMA-deficient HCT116 cells and CHOP-deficient mouse embryonic fibroblasts, but not in p53-deficient HCT116 cells. The results suggest the involvement of the p53-independent CHOP/PUMA axis in response to ferroptosis inducers, which may play a key role in ferroptotic agent-mediated sensitization to TRAIL-induced apoptosis. Impact Journals LLC 2017-12-08 /pmc/articles/PMC5777762/ /pubmed/29383150 http://dx.doi.org/10.18632/oncotarget.23046 Text en Copyright: © 2017 Hong et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Paper
Hong, Se Hoon
Lee, Dae-Hee
Lee, Young-Sun
Jo, Min Jee
Jeong, Yoon A
Kwon, William T.
Choudry, Haroon A.
Bartlett, David L.
Lee, Yong J.
Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression
title Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression
title_full Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression
title_fullStr Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression
title_full_unstemmed Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression
title_short Molecular crosstalk between ferroptosis and apoptosis: emerging role of ER stress-induced p53-independent PUMA expression
title_sort molecular crosstalk between ferroptosis and apoptosis: emerging role of er stress-induced p53-independent puma expression
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777762/
https://www.ncbi.nlm.nih.gov/pubmed/29383150
http://dx.doi.org/10.18632/oncotarget.23046
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