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Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells

Since its discovery, mitophagy has been viewed as a protective mechanism used by cancer cells to prevent the induction of mitochondrial apoptosis. Most cancer treatments directly or indirectly cause mitochondrial dysfunction in order to trigger signals for cell death. Elimination of these dysfunctio...

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Autores principales: Ahmadpour, Seyedeh Tayebeh, Desquiret-Dumas, Valérie, Yikilmaz, Ulku, Dartier, Julie, Domingo, Isabelle, Wetterwald, Celine, Orre, Charlotte, Gueguen, Naïg, Brisson, Lucie, Mahéo, Karine, Dumas, Jean-François
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431121/
https://www.ncbi.nlm.nih.gov/pubmed/34502189
http://dx.doi.org/10.3390/ijms22179283
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author Ahmadpour, Seyedeh Tayebeh
Desquiret-Dumas, Valérie
Yikilmaz, Ulku
Dartier, Julie
Domingo, Isabelle
Wetterwald, Celine
Orre, Charlotte
Gueguen, Naïg
Brisson, Lucie
Mahéo, Karine
Dumas, Jean-François
author_facet Ahmadpour, Seyedeh Tayebeh
Desquiret-Dumas, Valérie
Yikilmaz, Ulku
Dartier, Julie
Domingo, Isabelle
Wetterwald, Celine
Orre, Charlotte
Gueguen, Naïg
Brisson, Lucie
Mahéo, Karine
Dumas, Jean-François
author_sort Ahmadpour, Seyedeh Tayebeh
collection PubMed
description Since its discovery, mitophagy has been viewed as a protective mechanism used by cancer cells to prevent the induction of mitochondrial apoptosis. Most cancer treatments directly or indirectly cause mitochondrial dysfunction in order to trigger signals for cell death. Elimination of these dysfunctional mitochondria by mitophagy could thus prevent the initiation of the apoptotic cascade. In breast cancer patients, resistance to doxorubicin (DOX), one of the most widely used cancer drugs, is an important cause of poor clinical outcomes. However, the role played by mitophagy in the context of DOX resistance in breast cancer cells is not well understood. We therefore tried to determine whether an increase in mitophagic flux was associated with the resistance of breast cancer cells to DOX. Our first objective was to explore whether DOX-resistant breast cancer cells were characterized by conditions that favor mitophagy induction. We next tried to determine whether mitophagic flux was increased in DOX-resistant cells in response to DOX treatment. For this purpose, the parental (MCF-7) and DOX-resistant (MCF-7dox) breast cancer cell lines were used. Our results show that mitochondrial reactive oxygen species (ROS) production and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression are higher in MCF-7dox in a basal condition compared to MCF-7, suggesting DOX-resistant breast cancer cells are prone to stimuli to induce a mitophagy-related event. Our results also showed that, in response to DOX, autophagolysosome formation is induced in DOX-resistant breast cancer cells. This mitophagic step following DOX treatment seems to be partly due to mitochondrial ROS production as autophagolysosome formation is moderately decreased by the mitochondrial antioxidant mitoTEMPO.
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spelling pubmed-84311212021-09-11 Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells Ahmadpour, Seyedeh Tayebeh Desquiret-Dumas, Valérie Yikilmaz, Ulku Dartier, Julie Domingo, Isabelle Wetterwald, Celine Orre, Charlotte Gueguen, Naïg Brisson, Lucie Mahéo, Karine Dumas, Jean-François Int J Mol Sci Article Since its discovery, mitophagy has been viewed as a protective mechanism used by cancer cells to prevent the induction of mitochondrial apoptosis. Most cancer treatments directly or indirectly cause mitochondrial dysfunction in order to trigger signals for cell death. Elimination of these dysfunctional mitochondria by mitophagy could thus prevent the initiation of the apoptotic cascade. In breast cancer patients, resistance to doxorubicin (DOX), one of the most widely used cancer drugs, is an important cause of poor clinical outcomes. However, the role played by mitophagy in the context of DOX resistance in breast cancer cells is not well understood. We therefore tried to determine whether an increase in mitophagic flux was associated with the resistance of breast cancer cells to DOX. Our first objective was to explore whether DOX-resistant breast cancer cells were characterized by conditions that favor mitophagy induction. We next tried to determine whether mitophagic flux was increased in DOX-resistant cells in response to DOX treatment. For this purpose, the parental (MCF-7) and DOX-resistant (MCF-7dox) breast cancer cell lines were used. Our results show that mitochondrial reactive oxygen species (ROS) production and hypoxia-inducible factor-1 alpha (HIF-1 alpha) expression are higher in MCF-7dox in a basal condition compared to MCF-7, suggesting DOX-resistant breast cancer cells are prone to stimuli to induce a mitophagy-related event. Our results also showed that, in response to DOX, autophagolysosome formation is induced in DOX-resistant breast cancer cells. This mitophagic step following DOX treatment seems to be partly due to mitochondrial ROS production as autophagolysosome formation is moderately decreased by the mitochondrial antioxidant mitoTEMPO. MDPI 2021-08-27 /pmc/articles/PMC8431121/ /pubmed/34502189 http://dx.doi.org/10.3390/ijms22179283 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahmadpour, Seyedeh Tayebeh
Desquiret-Dumas, Valérie
Yikilmaz, Ulku
Dartier, Julie
Domingo, Isabelle
Wetterwald, Celine
Orre, Charlotte
Gueguen, Naïg
Brisson, Lucie
Mahéo, Karine
Dumas, Jean-François
Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells
title Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells
title_full Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells
title_fullStr Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells
title_full_unstemmed Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells
title_short Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells
title_sort doxorubicin-induced autophagolysosome formation is partly prevented by mitochondrial ros elimination in dox-resistant breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431121/
https://www.ncbi.nlm.nih.gov/pubmed/34502189
http://dx.doi.org/10.3390/ijms22179283
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