Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer
IntroductionOvarian cancer is one of the leading causes of death for women with cancer worldwide. Energy requirements for tumor growth in epithelial high-grade serous ovarian cancer (HGSOC) are fulfilled by a combination of aerobic glycolysis and oxidative phosphorylation (OXPHOS). Although reduced...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1129352/full |
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| author | Zeynep C. Koc Vincent E. Sollars Nadim Bou Zgheib Gary O. Rankin Emine C. Koc |
| author_facet | Zeynep C. Koc Vincent E. Sollars Nadim Bou Zgheib Gary O. Rankin Emine C. Koc |
| author_sort | Zeynep C. Koc |
| collection | DOAJ |
| description | IntroductionOvarian cancer is one of the leading causes of death for women with cancer worldwide. Energy requirements for tumor growth in epithelial high-grade serous ovarian cancer (HGSOC) are fulfilled by a combination of aerobic glycolysis and oxidative phosphorylation (OXPHOS). Although reduced OXPHOS activity has emerged as one of the significant contributors to tumor aggressiveness and chemoresistance, up-regulation of mitochondrial antioxidant capacity is required for matrix detachment and colonization into the peritoneal cavity to form malignant ascites in HGSOC patients. However, limited information is available about the mitochondrial biogenesis regulating OXPHOS capacity and generation of mitochondrial reactive oxygen species (mtROS) in HGSOC.MethodsTo evaluate the modulation of OXPHOS in HGSOC tumor samples and ovarian cancer cell lines, we performed proteomic analyses of proteins involved in mitochondrial energy metabolism and biogenesis and formation of mtROS by immunoblotting and flow cytometry, respectively.Results and discussionWe determined that the increased steady-state expression levels of mitochondrial- and nuclear-encoded OXPHOS subunits were associated with increased mitochondrial biogenesis in HGSOC tumors and ovarian cancer cell lines. The more prominent increase in MT-COII expression was in agreement with significant increase in mitochondrial translation factors, TUFM and DARS2. On the other hand, the ovarian cancer cell lines with reduced OXPHOS subunit expression and mitochondrial translation generated the highest levels of mtROS and significantly reduced SOD2 expression. Evaluation of mitochondrial biogenesis suggested that therapies directed against mitochondrial targets, such as those involved in transcription and translation machineries, should be considered in addition to the conventional chemotherapies in HGSOC treatment. |
| first_indexed | 2024-04-10T06:32:27Z |
| format | Article |
| id | doaj.art-f218794147364829983a3154f0345539 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-10T06:32:27Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f218794147364829983a3154f03455392023-03-01T07:03:21ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-03-011310.3389/fonc.2023.11293521129352Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancerZeynep C. Koc0Vincent E. Sollars1Nadim Bou Zgheib2Gary O. Rankin3Emine C. Koc4Department of Obstetrics, Gynecology and Reproductive Sciences, Temple University, Philadelphia, PA, United StatesDepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesEdwards Comprehensive Cancer Center, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesDepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesDepartment of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United StatesIntroductionOvarian cancer is one of the leading causes of death for women with cancer worldwide. Energy requirements for tumor growth in epithelial high-grade serous ovarian cancer (HGSOC) are fulfilled by a combination of aerobic glycolysis and oxidative phosphorylation (OXPHOS). Although reduced OXPHOS activity has emerged as one of the significant contributors to tumor aggressiveness and chemoresistance, up-regulation of mitochondrial antioxidant capacity is required for matrix detachment and colonization into the peritoneal cavity to form malignant ascites in HGSOC patients. However, limited information is available about the mitochondrial biogenesis regulating OXPHOS capacity and generation of mitochondrial reactive oxygen species (mtROS) in HGSOC.MethodsTo evaluate the modulation of OXPHOS in HGSOC tumor samples and ovarian cancer cell lines, we performed proteomic analyses of proteins involved in mitochondrial energy metabolism and biogenesis and formation of mtROS by immunoblotting and flow cytometry, respectively.Results and discussionWe determined that the increased steady-state expression levels of mitochondrial- and nuclear-encoded OXPHOS subunits were associated with increased mitochondrial biogenesis in HGSOC tumors and ovarian cancer cell lines. The more prominent increase in MT-COII expression was in agreement with significant increase in mitochondrial translation factors, TUFM and DARS2. On the other hand, the ovarian cancer cell lines with reduced OXPHOS subunit expression and mitochondrial translation generated the highest levels of mtROS and significantly reduced SOD2 expression. Evaluation of mitochondrial biogenesis suggested that therapies directed against mitochondrial targets, such as those involved in transcription and translation machineries, should be considered in addition to the conventional chemotherapies in HGSOC treatment.https://www.frontiersin.org/articles/10.3389/fonc.2023.1129352/fullmitochondrial biogenesismitochondrial translation and transcriptionmitochondrial reactive oxygen species (mtROS)oxidative phosphorylation (OXPHOS)high-grade serous ovarian cancer (HGSOC)MT-COII |
| spellingShingle | Zeynep C. Koc Vincent E. Sollars Nadim Bou Zgheib Gary O. Rankin Emine C. Koc Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer Frontiers in Oncology mitochondrial biogenesis mitochondrial translation and transcription mitochondrial reactive oxygen species (mtROS) oxidative phosphorylation (OXPHOS) high-grade serous ovarian cancer (HGSOC) MT-COII |
| title | Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer |
| title_full | Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer |
| title_fullStr | Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer |
| title_full_unstemmed | Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer |
| title_short | Evaluation of mitochondrial biogenesis and ROS generation in high-grade serous ovarian cancer |
| title_sort | evaluation of mitochondrial biogenesis and ros generation in high grade serous ovarian cancer |
| topic | mitochondrial biogenesis mitochondrial translation and transcription mitochondrial reactive oxygen species (mtROS) oxidative phosphorylation (OXPHOS) high-grade serous ovarian cancer (HGSOC) MT-COII |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1129352/full |
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