The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy
Cancer is one of the world’s deadliest afflictions. Despite recent advances in diagnostic and surgical technologies, as well as improved treatments of some individual tumor types, there is currently no universal cure to prevent or impede the uncontrolled proliferation of malignant cells. Targeting t...
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| Format: | Article |
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MDPI AG
2021-01-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/10/1/33 |
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| author | Jan Ježek Katrina F. Cooper Randy Strich |
| author_facet | Jan Ježek Katrina F. Cooper Randy Strich |
| author_sort | Jan Ježek |
| collection | DOAJ |
| description | Cancer is one of the world’s deadliest afflictions. Despite recent advances in diagnostic and surgical technologies, as well as improved treatments of some individual tumor types, there is currently no universal cure to prevent or impede the uncontrolled proliferation of malignant cells. Targeting tumors by inducing apoptosis is one of the pillars of cancer treatment. Changes in mitochondrial morphology precede intrinsic apoptosis, but mitochondrial dynamics has only recently been recognized as a viable pharmacological target. In many cancers, oncogenic transformation is accompanied by accumulation of elevated cellular levels of ROS leading to redox imbalance. Hence, a common chemotherapeutic strategy against such tumor types involves deploying pro-oxidant agents to increase ROS levels above an apoptotic death-inducing threshold. The aim of this chapter is to investigate the benefit of stimulating mitochondrial fission-dependent production of ROS for enhanced killing of solid tumors. The main question to be addressed is whether a sudden and abrupt change in mitochondrial shape toward the fragmented phenotype can be pharmacologically harnessed to trigger a burst of mitochondrial ROS sufficient to initiate apoptosis specifically in cancer cells but not in non-transformed healthy tissues. |
| first_indexed | 2024-03-10T13:27:14Z |
| format | Article |
| id | doaj.art-92bc613d9a2b416da30043c184e409e8 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T13:27:14Z |
| publishDate | 2021-01-01 |
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| spelling | doaj.art-92bc613d9a2b416da30043c184e409e82023-11-21T08:55:38ZengMDPI AGBiology2079-77372021-01-011013310.3390/biology10010033The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic ChemotherapyJan Ježek0Katrina F. Cooper1Randy Strich2The Wellcome Trust/Gurdon Cancer Research Institute, University of Cambridge, Cambridge CB2 1QN, UKDepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USADepartment of Molecular Biology, School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USACancer is one of the world’s deadliest afflictions. Despite recent advances in diagnostic and surgical technologies, as well as improved treatments of some individual tumor types, there is currently no universal cure to prevent or impede the uncontrolled proliferation of malignant cells. Targeting tumors by inducing apoptosis is one of the pillars of cancer treatment. Changes in mitochondrial morphology precede intrinsic apoptosis, but mitochondrial dynamics has only recently been recognized as a viable pharmacological target. In many cancers, oncogenic transformation is accompanied by accumulation of elevated cellular levels of ROS leading to redox imbalance. Hence, a common chemotherapeutic strategy against such tumor types involves deploying pro-oxidant agents to increase ROS levels above an apoptotic death-inducing threshold. The aim of this chapter is to investigate the benefit of stimulating mitochondrial fission-dependent production of ROS for enhanced killing of solid tumors. The main question to be addressed is whether a sudden and abrupt change in mitochondrial shape toward the fragmented phenotype can be pharmacologically harnessed to trigger a burst of mitochondrial ROS sufficient to initiate apoptosis specifically in cancer cells but not in non-transformed healthy tissues.https://www.mdpi.com/2079-7737/10/1/33mitochondriareactive oxygen speciescancerchemotherapyoxidative stressstress signaling |
| spellingShingle | Jan Ježek Katrina F. Cooper Randy Strich The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy Biology mitochondria reactive oxygen species cancer chemotherapy oxidative stress stress signaling |
| title | The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy |
| title_full | The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy |
| title_fullStr | The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy |
| title_full_unstemmed | The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy |
| title_short | The Impact of Mitochondrial Fission-Stimulated ROS Production on Pro-Apoptotic Chemotherapy |
| title_sort | impact of mitochondrial fission stimulated ros production on pro apoptotic chemotherapy |
| topic | mitochondria reactive oxygen species cancer chemotherapy oxidative stress stress signaling |
| url | https://www.mdpi.com/2079-7737/10/1/33 |
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