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Article Abstract
Background: The anthracycline anticancer drug doxorubicin (DOX) induces myocardial cell death and heart failure. The aim of the present study was to investigate whether nobiletin (NOB), a natural flavonoid isolated from citrus peel, has a protective effect against DOX-induced cardiotoxicity.
Methods And Results: H9C2 cells were pretreated with 100 μM NOB and then treated with 1 μM DOX. An MTT assay revealed that NOB improved the decreased cell viability induced by DOX. A TUNEL assay showed that NOB treatment improved DOX-induced apoptosis in H9C2 cells. Western blotting indicated that DOX-induced increases in cleaved caspase-3 and -9 expression were significantly suppressed by NOB treatment. Motion field imaging of human iPS cell-derived cardiomyocyte sheets showed that NOB significantly suppressed a DOX-induced reduction of their contractile function. Next, to investigate the effect of NOB in vivo, DOX was intraperitoneally administered to mice. Echocardiography showed that oral administration of NOB reduced DOX-induced left ventricular systolic dysfunction, and a TUNEL assay showed that oral administration also inhibited apoptosis in the mouse heart.
Conclusions: These results indicate that NOB treatment suppressed DOX-induced cardiotoxicity by reducing apoptosis. Further study of the mechanism of this effect may lead to the development of a novel therapy for DOX-induced heart failure.
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| http://dx.doi.org/10.1016/j.jphs.2025.03.011 | DOI Listing |
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