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Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma

Recent data have indicated a fundamental role of iron in mediating a non-apoptotic and non-necrotic oxidative form of programmed cell death termed ferroptosis that requires abundant cytosolic free labile iron to promote membrane lipid peroxidation. Different scavenger molecules and detoxifying enzym...

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Autores principales: Fanzani, Alessandro, Poli, Maura
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578108/
https://www.ncbi.nlm.nih.gov/pubmed/28783123
http://dx.doi.org/10.3390/ijms18081718
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author Fanzani, Alessandro
Poli, Maura
author_facet Fanzani, Alessandro
Poli, Maura
author_sort Fanzani, Alessandro
collection PubMed
description Recent data have indicated a fundamental role of iron in mediating a non-apoptotic and non-necrotic oxidative form of programmed cell death termed ferroptosis that requires abundant cytosolic free labile iron to promote membrane lipid peroxidation. Different scavenger molecules and detoxifying enzymes, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), have been shown to overwhelm or exacerbate ferroptosis depending on their expression magnitude. Ferroptosis is emerging as a potential weapon against tumor growth since it has been shown to potentiate cell death in some malignancies. However, this mechanism has been poorly studied in Rhabdomyosarcoma (RMS), a myogenic tumor affecting childhood and adolescence. One of the main drivers of RMS genesis is the Retrovirus Associated DNA Sequences/Extracellular signal Regulated Kinases (RAS/ERK)signaling pathway, the deliberate activation of which correlates with tumor aggressiveness and oxidative stress levels. Since recent studies have indicated that treatment with oxidative inducers can significantly halt RMS tumor progression, in this review we covered different aspects, ranging from iron metabolism in carcinogenesis and tumor growth, to mechanisms of iron-mediated cell death, to highlight the potential role of ferroptosis in counteracting RMS growth.
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spelling pubmed-55781082017-09-05 Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma Fanzani, Alessandro Poli, Maura Int J Mol Sci Review Recent data have indicated a fundamental role of iron in mediating a non-apoptotic and non-necrotic oxidative form of programmed cell death termed ferroptosis that requires abundant cytosolic free labile iron to promote membrane lipid peroxidation. Different scavenger molecules and detoxifying enzymes, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), have been shown to overwhelm or exacerbate ferroptosis depending on their expression magnitude. Ferroptosis is emerging as a potential weapon against tumor growth since it has been shown to potentiate cell death in some malignancies. However, this mechanism has been poorly studied in Rhabdomyosarcoma (RMS), a myogenic tumor affecting childhood and adolescence. One of the main drivers of RMS genesis is the Retrovirus Associated DNA Sequences/Extracellular signal Regulated Kinases (RAS/ERK)signaling pathway, the deliberate activation of which correlates with tumor aggressiveness and oxidative stress levels. Since recent studies have indicated that treatment with oxidative inducers can significantly halt RMS tumor progression, in this review we covered different aspects, ranging from iron metabolism in carcinogenesis and tumor growth, to mechanisms of iron-mediated cell death, to highlight the potential role of ferroptosis in counteracting RMS growth. MDPI 2017-08-07 /pmc/articles/PMC5578108/ /pubmed/28783123 http://dx.doi.org/10.3390/ijms18081718 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fanzani, Alessandro
Poli, Maura
Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
title Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
title_full Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
title_fullStr Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
title_full_unstemmed Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
title_short Iron, Oxidative Damage and Ferroptosis in Rhabdomyosarcoma
title_sort iron, oxidative damage and ferroptosis in rhabdomyosarcoma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578108/
https://www.ncbi.nlm.nih.gov/pubmed/28783123
http://dx.doi.org/10.3390/ijms18081718
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