Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer
Abstract Introduction Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models...
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| Format: | Article |
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BMC
2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-025-06108-y |
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| author | Tytti-Maria Uurasmaa Pauline Bourdin Wail Nammas Shiva Latifi Heidi Liljenbäck Antti Saraste Olli Eskola Johan Rajander Anne Roivainen Helene Rundqvist Anu Autio Ilkka Heinonen Katja Anttila |
| author_facet | Tytti-Maria Uurasmaa Pauline Bourdin Wail Nammas Shiva Latifi Heidi Liljenbäck Antti Saraste Olli Eskola Johan Rajander Anne Roivainen Helene Rundqvist Anu Autio Ilkka Heinonen Katja Anttila |
| author_sort | Tytti-Maria Uurasmaa |
| collection | DOAJ |
| description | Abstract Introduction Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear. Objectives This study investigated ET-induced structural, functional, vascular, oxidative stress, and plausible glucose uptake alterations of the left ventricle (LV) in a murine breast cancer model during DOX treatment. Methods Female FVB/N-mice were divided to tumor-free groups with or without voluntary wheel-running ET and those inoculated subcutaneously with mammary tumor-derived I3TC-cells with or without exercise or DOX treatment (5 mg/kg/week). Mice underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography and echocardiography after two and four DOX-doses. The cardiac histology, oxidative stress, maximal metabolic enzyme activities, and mitochondrial respiration were analyzed. Results DOX increased LV glucose uptake (LVGU) and mitochondrial uncoupling and decreased running activity, LV-weight, and ejection fraction (EF). In DOX-treated group ET blunted the increase in LVGU, increased LV-weight and EF, and lowered LV lactate dehydrogenase activity. DOX-treated exercised mice did not differ from tumor-bearing group without DOX in LVGU or from the tumor-free ET-group in LV-weight or EF whereas unexercised DOX-treated group did. ET also increased LV citrate synthase activity in tumor-bearing animals. There was an inverse association between LVGU and EF and LV-weight. Conclusion In a murine breast cancer model, voluntary ET moderated DOX-induced cardiotoxicities such as increased LVGU, LV-atrophy and decreased EF. This suggests that ET might benefit patients with cancer undergoing doxorubicin treatment by mitigating cardiotoxicity. |
| format | Article |
| id | doaj-art-d10e09af642b48a3b54731fed5c8f2fe |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj-art-d10e09af642b48a3b54731fed5c8f2fe2025-01-26T12:50:06ZengBMCJournal of Translational Medicine1479-58762025-01-0123111310.1186/s12967-025-06108-yExercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancerTytti-Maria Uurasmaa0Pauline Bourdin1Wail Nammas2Shiva Latifi3Heidi Liljenbäck4Antti Saraste5Olli Eskola6Johan Rajander7Anne Roivainen8Helene Rundqvist9Anu Autio10Ilkka Heinonen11Katja Anttila12Department of Biology, University of TurkuDepartment of Biology, University of TurkuTurku PET Centre, University of Turku, Turku University HospitalDepartment of Biology, University of TurkuTurku PET Centre, University of Turku, Turku University HospitalTurku PET Centre, University of Turku, Turku University HospitalTurku PET Centre, University of Turku, Turku University HospitalAccelerator Laboratory, Åbo Akademi UniversityTurku PET Centre, University of Turku, Turku University HospitalDepartment of Laboratory Medicine, Karolinska InstituteTurku PET Centre, University of Turku, Turku University HospitalTurku PET Centre, University of Turku, Turku University HospitalDepartment of Biology, University of TurkuAbstract Introduction Doxorubicin is a chemotherapeutic drug used to treat various cancers. Exercise training (ET) can attenuate some cardiotoxic effects of doxorubicin (DOX) in tumor-free animals. However, the ET effects on cardiac function and glucose metabolism in DOX-treated breast cancer models remain unclear. Objectives This study investigated ET-induced structural, functional, vascular, oxidative stress, and plausible glucose uptake alterations of the left ventricle (LV) in a murine breast cancer model during DOX treatment. Methods Female FVB/N-mice were divided to tumor-free groups with or without voluntary wheel-running ET and those inoculated subcutaneously with mammary tumor-derived I3TC-cells with or without exercise or DOX treatment (5 mg/kg/week). Mice underwent 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography and echocardiography after two and four DOX-doses. The cardiac histology, oxidative stress, maximal metabolic enzyme activities, and mitochondrial respiration were analyzed. Results DOX increased LV glucose uptake (LVGU) and mitochondrial uncoupling and decreased running activity, LV-weight, and ejection fraction (EF). In DOX-treated group ET blunted the increase in LVGU, increased LV-weight and EF, and lowered LV lactate dehydrogenase activity. DOX-treated exercised mice did not differ from tumor-bearing group without DOX in LVGU or from the tumor-free ET-group in LV-weight or EF whereas unexercised DOX-treated group did. ET also increased LV citrate synthase activity in tumor-bearing animals. There was an inverse association between LVGU and EF and LV-weight. Conclusion In a murine breast cancer model, voluntary ET moderated DOX-induced cardiotoxicities such as increased LVGU, LV-atrophy and decreased EF. This suggests that ET might benefit patients with cancer undergoing doxorubicin treatment by mitigating cardiotoxicity.https://doi.org/10.1186/s12967-025-06108-yGlucose metabolismCardiotoxicityExerciseAnthracyclinesCSLDH |
| spellingShingle | Tytti-Maria Uurasmaa Pauline Bourdin Wail Nammas Shiva Latifi Heidi Liljenbäck Antti Saraste Olli Eskola Johan Rajander Anne Roivainen Helene Rundqvist Anu Autio Ilkka Heinonen Katja Anttila Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer Journal of Translational Medicine Glucose metabolism Cardiotoxicity Exercise Anthracyclines CS LDH |
| title | Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer |
| title_full | Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer |
| title_fullStr | Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer |
| title_full_unstemmed | Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer |
| title_short | Exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer |
| title_sort | exercise training partly ameliorates cardiac dysfunction in mice during doxorubicin treatment of breast cancer |
| topic | Glucose metabolism Cardiotoxicity Exercise Anthracyclines CS LDH |
| url | https://doi.org/10.1186/s12967-025-06108-y |
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