Natural product as a lead for impairing mitochondrial respiration in cancer cells
The impact of the isoxazole derivative of usnic acid, ISOXUS (formerly known as 2b) on cancer and non-cancerous cell metabolism was investigated. ISOXUS significantly reduced the utilisation of most metabolic substrates that produce NADH or FADH2, mitochondrial electron flow and oxygen consumption r...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2025.2465575 |
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| author | Agnieszka Pyrczak-Felczykowska Anna-Karina Kaczorowska Artur Giełdoń Alicja Braczko Ryszard T. Smoleński Jędrzej Antosiewicz Tristan A. Reekie Anna Herman-Antosiewicz |
| author_facet | Agnieszka Pyrczak-Felczykowska Anna-Karina Kaczorowska Artur Giełdoń Alicja Braczko Ryszard T. Smoleński Jędrzej Antosiewicz Tristan A. Reekie Anna Herman-Antosiewicz |
| author_sort | Agnieszka Pyrczak-Felczykowska |
| collection | DOAJ |
| description | The impact of the isoxazole derivative of usnic acid, ISOXUS (formerly known as 2b) on cancer and non-cancerous cell metabolism was investigated. ISOXUS significantly reduced the utilisation of most metabolic substrates that produce NADH or FADH2, mitochondrial electron flow and oxygen consumption rate (OCR) in MCF-7 breast cancer cells in contrast to HB2 normal epithelial cells. Molecular docking revealed that ISOXUS inhibits mitochondrial respiratory chain complex II, which was confirmed experimentally. Disturbance of electron flow in MCF-7 cells resulted in increased reactive oxygen species (ROS) production. They appeared crucial for ISOXUS-induced cancer cell vacuolization and a drop in survival as an antioxidant, α-tocopherol, protected against these processes. These findings indicate that ISOXUS is a metabolic inhibitor that targets mitochondrial complex II in breast cancer cells resulting in diminished ATP production and increased ROS formation which translates into reduced cell viability. |
| format | Article |
| id | doaj-art-25b9b6ea72ef4bd099219202115a38ed |
| institution | OA Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-25b9b6ea72ef4bd099219202115a38ed2025-08-20T02:30:13ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2025.2465575Natural product as a lead for impairing mitochondrial respiration in cancer cellsAgnieszka Pyrczak-Felczykowska0Anna-Karina Kaczorowska1Artur Giełdoń2Alicja Braczko3Ryszard T. Smoleński4Jędrzej Antosiewicz5Tristan A. Reekie6Anna Herman-Antosiewicz7Department of Physiology, Medical University of Gdańsk, Gdańsk, PolandFaculty of Biology, Collection of Plasmids and Microorganisms, University of Gdańsk, Gdańsk, PolandDepartment of Theoretical Chemistry, Faculty of Chemistry, University of Gdańsk, Gdańsk, PolandDepartment of Biochemistry, Medical University of Gdańsk, Gdańsk, PolandDepartment of Biochemistry, Medical University of Gdańsk, Gdańsk, PolandDepartment of Bioenergetics and Exercise Physiology, Medical University of Gdańsk, Gdańsk, PolandSchool of Science, University of New South Wales Canberra, Canberra, AustraliaDepartment of Medical Biology and Genetics, Faculty of Biology, University of Gdańsk, Gdańsk, PolandThe impact of the isoxazole derivative of usnic acid, ISOXUS (formerly known as 2b) on cancer and non-cancerous cell metabolism was investigated. ISOXUS significantly reduced the utilisation of most metabolic substrates that produce NADH or FADH2, mitochondrial electron flow and oxygen consumption rate (OCR) in MCF-7 breast cancer cells in contrast to HB2 normal epithelial cells. Molecular docking revealed that ISOXUS inhibits mitochondrial respiratory chain complex II, which was confirmed experimentally. Disturbance of electron flow in MCF-7 cells resulted in increased reactive oxygen species (ROS) production. They appeared crucial for ISOXUS-induced cancer cell vacuolization and a drop in survival as an antioxidant, α-tocopherol, protected against these processes. These findings indicate that ISOXUS is a metabolic inhibitor that targets mitochondrial complex II in breast cancer cells resulting in diminished ATP production and increased ROS formation which translates into reduced cell viability.https://www.tandfonline.com/doi/10.1080/14756366.2025.2465575Lichensusnic acidbreast cancerelectron transport chaincomplex II |
| spellingShingle | Agnieszka Pyrczak-Felczykowska Anna-Karina Kaczorowska Artur Giełdoń Alicja Braczko Ryszard T. Smoleński Jędrzej Antosiewicz Tristan A. Reekie Anna Herman-Antosiewicz Natural product as a lead for impairing mitochondrial respiration in cancer cells Journal of Enzyme Inhibition and Medicinal Chemistry Lichens usnic acid breast cancer electron transport chain complex II |
| title | Natural product as a lead for impairing mitochondrial respiration in cancer cells |
| title_full | Natural product as a lead for impairing mitochondrial respiration in cancer cells |
| title_fullStr | Natural product as a lead for impairing mitochondrial respiration in cancer cells |
| title_full_unstemmed | Natural product as a lead for impairing mitochondrial respiration in cancer cells |
| title_short | Natural product as a lead for impairing mitochondrial respiration in cancer cells |
| title_sort | natural product as a lead for impairing mitochondrial respiration in cancer cells |
| topic | Lichens usnic acid breast cancer electron transport chain complex II |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2025.2465575 |
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