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Ferroptosis: An emerging therapeutic opportunity for cancer

Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can...

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Detalles Bibliográficos
Autores principales: Wang, Liyuan, Chen, Xiaoguang, Yan, Chunhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chongqing Medical University 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843872/
https://www.ncbi.nlm.nih.gov/pubmed/35224150
http://dx.doi.org/10.1016/j.gendis.2020.09.005
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author Wang, Liyuan
Chen, Xiaoguang
Yan, Chunhong
author_facet Wang, Liyuan
Chen, Xiaoguang
Yan, Chunhong
author_sort Wang, Liyuan
collection PubMed
description Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation, thereby suppressing ferroptosis. Indeed, RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly, erastin and other system Xc(−) inhibitors can deplete intracellular glutathione required for GPX4 function, leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens, the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis, but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents, which include system Xc(−) inhibitors, GPX4 inhibitors, and iron-based nanoparticles, in cancer therapy will be subsequently discussed.
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spelling pubmed-88438722022-02-25 Ferroptosis: An emerging therapeutic opportunity for cancer Wang, Liyuan Chen, Xiaoguang Yan, Chunhong Genes Dis Review Article Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation, thereby suppressing ferroptosis. Indeed, RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly, erastin and other system Xc(−) inhibitors can deplete intracellular glutathione required for GPX4 function, leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens, the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis, but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents, which include system Xc(−) inhibitors, GPX4 inhibitors, and iron-based nanoparticles, in cancer therapy will be subsequently discussed. Chongqing Medical University 2020-09-29 /pmc/articles/PMC8843872/ /pubmed/35224150 http://dx.doi.org/10.1016/j.gendis.2020.09.005 Text en © 2020 Chongqing Medical University. Production and hosting by Elsevier B.V. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Review Article
Wang, Liyuan
Chen, Xiaoguang
Yan, Chunhong
Ferroptosis: An emerging therapeutic opportunity for cancer
title Ferroptosis: An emerging therapeutic opportunity for cancer
title_full Ferroptosis: An emerging therapeutic opportunity for cancer
title_fullStr Ferroptosis: An emerging therapeutic opportunity for cancer
title_full_unstemmed Ferroptosis: An emerging therapeutic opportunity for cancer
title_short Ferroptosis: An emerging therapeutic opportunity for cancer
title_sort ferroptosis: an emerging therapeutic opportunity for cancer
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843872/
https://www.ncbi.nlm.nih.gov/pubmed/35224150
http://dx.doi.org/10.1016/j.gendis.2020.09.005
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