Marein Alleviates Doxorubicin-Induced Cardiotoxicity through FAK/AKT Pathway Modulation while Potentiating its Anticancer Activity.

Autor: Xu J; Department of Cardiology, Huanggang Central Hospital, Huanggang, China. 18986552877@163.com., Lv M; Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China., Ni X; Department of Neurology, Huanggang Central Hospital, Huanggang, China.
Jazyk: angličtina
Zdroj: Cardiovascular toxicology [Cardiovasc Toxicol] 2024 Aug; Vol. 24 (8), pp. 818-835. Date of Electronic Publication: 2024 Jun 19.
DOI: 10.1007/s12012-024-09882-1
Abstrakt: Doxorubicin (DOX) is an effective anticancer agent, yet its clinical utility is hampered by dose-dependent cardiotoxicity. This study explores the cardioprotective potential of Marein (Mar) against DOX-induced cardiac injury and elucidates underlying molecular mechanisms. Neonatal rat cardiomyocytes (NRCMs) and murine models were employed to assess the impact of Mar on DOX-induced cardiotoxicity (DIC). In vitro, cell viability, oxidative stress were evaluated. In vivo, a chronic injection method was employed to induce a DIC mouse model, followed by eight weeks of Mar treatment. Cardiac function, histopathology, and markers of cardiotoxicity were assessed. In vitro, Mar treatment demonstrated significant cardioprotective effects in vivo, as evidenced by improved cardiac function and reduced indicators of cardiac damage. Mechanistically, Mar reduced inflammation, oxidative stress, and apoptosis in cardiomyocytes, potentially via activation of the Focal Adhesion Kinase (FAK)/AKT pathway. Mar also exhibited an anti-ferroptosis effect. Interestingly, Mar did not compromise DOX's efficacy in cancer cells, suggesting a dual benefit in onco-cardiology. Molecular docking studies suggested a potential interaction between Mar and FAK. This study demonstrates Mar's potential as a mitigator of DOX-induced cardiotoxicity, offering a translational perspective on its clinical application. By activating the FAK/AKT pathway, Mar exerts protective effects against DOX-induced cardiomyocyte damage, highlighting its promise in onco-cardiology. Further research is warranted to validate these findings and advance Mar as a potential adjunctive therapy in cancer treatment.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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