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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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/17/9283 |
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| author | Seyedeh Tayebeh Ahmadpour Valérie Desquiret-Dumas Ulku Yikilmaz Julie Dartier Isabelle Domingo Celine Wetterwald Charlotte Orre Naïg Gueguen Lucie Brisson Karine Mahéo Jean-François Dumas |
| author_facet | Seyedeh Tayebeh Ahmadpour Valérie Desquiret-Dumas Ulku Yikilmaz Julie Dartier Isabelle Domingo Celine Wetterwald Charlotte Orre Naïg Gueguen Lucie Brisson Karine Mahéo Jean-François Dumas |
| author_sort | Seyedeh Tayebeh Ahmadpour |
| collection | DOAJ |
| 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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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:11:38Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5e6e9ed51d0041baa139dbad6d4a8cb52023-11-22T10:40:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012217928310.3390/ijms22179283Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer CellsSeyedeh Tayebeh Ahmadpour0Valérie Desquiret-Dumas1Ulku Yikilmaz2Julie Dartier3Isabelle Domingo4Celine Wetterwald5Charlotte Orre6Naïg Gueguen7Lucie Brisson8Karine Mahéo9Jean-François Dumas10Inserm UMR1069 Nutrition, Croissance et Cancer, Université de Tours, 37032 Tours, FranceMitoLab Team, Institut MitoVasc, CNRS UMR6015, INSERM U1083, Angers University, 49933 Angers, FranceInserm UMR1069 Nutrition, Croissance et Cancer, Université de Tours, 37032 Tours, FranceInserm UMR1069 Nutrition, Croissance et Cancer, Université de Tours, 37032 Tours, FranceInserm UMR1069 Nutrition, Croissance et Cancer, Université de Tours, 37032 Tours, FranceDepartment of Biochemistry and Molecular Biology, University Hospital Angers, 49933 Angers, FranceMitoLab Team, Institut MitoVasc, CNRS UMR6015, INSERM U1083, Angers University, 49933 Angers, FranceMitoLab Team, Institut MitoVasc, CNRS UMR6015, INSERM U1083, Angers University, 49933 Angers, FranceInserm UMR1069 Nutrition, Croissance et Cancer, Université de Tours, 37032 Tours, FranceInserm UMR1069 Nutrition, Croissance et Cancer, Université de Tours, 37032 Tours, FranceInserm UMR1069 Nutrition, Croissance et Cancer, Université de Tours, 37032 Tours, FranceSince 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.https://www.mdpi.com/1422-0067/22/17/9283mitochondriamitophagybreast cancerreactive oxygen speciesdoxorubicin |
| spellingShingle | Seyedeh Tayebeh Ahmadpour Valérie Desquiret-Dumas Ulku Yikilmaz Julie Dartier Isabelle Domingo Celine Wetterwald Charlotte Orre Naïg Gueguen Lucie Brisson Karine Mahéo Jean-François Dumas Doxorubicin-Induced Autophagolysosome Formation Is Partly Prevented by Mitochondrial ROS Elimination in DOX-Resistant Breast Cancer Cells International Journal of Molecular Sciences mitochondria mitophagy breast cancer reactive oxygen species doxorubicin |
| 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 | mitochondria mitophagy breast cancer reactive oxygen species doxorubicin |
| url | https://www.mdpi.com/1422-0067/22/17/9283 |
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