Chrysanthemum morifolium Extract Ameliorates Doxorubicin-Induced Cardiotoxicity by Decreasing Apoptosis

SIMPLE SUMMARY: The anticancer drug doxorubicin is widely used for the treatment of malignant tumors, including colon, breast, and ovary cancers. However, prolonged use of doxorubicin causes heart damage, ranging from changes in the structure and function of heart cells to heart failure, the condition in which the heart does not pump enough blood. As this problem affects the quality of life and survival of cancer patients, solutions to it are urgently needed. This study demonstrates that Chrysanthemum morifolium extract, an extract of the purple chrysanthemum flower, reduced the heart damage caused by doxorubicin by suppressing cell death in heart cells and heart failure in an animal model. As Chrysanthemum morifolium has been eaten since ancient times, the extract from this functional food is likely to be safe in clinical application, potentially allowing patients to receive the well-established anti-cancer benefits of doxorubicin without the side effect of heart damage. ABSTRACT: It is well known that the anthracycline anticancer drug doxorubicin (DOX) induces cardiotoxicity. Recently, Chrysanthemum morifolium extract (CME), an extract of the purple chrysanthemum flower, has been reported to possess various physiological activities such as antioxidant and anti-inflammatory effects. However, its effect on DOX-induced cardiotoxicity is still unknown. An 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT)assay revealed that 1 mg/mL of CME reduced DOX-induced cytotoxicity in H9C2 cells but not in MDA-MB-231 cells. A TUNEL assay indicated that CME treatment improved DOX-induced apoptosis in H9C2 cells. Moreover, DOX-induced increases in the expression levels of p53, phosphorylated p53, and cleaved caspase-3,9 were significantly suppressed by CME treatment. Next, we investigated the effect of CME in vivo. The results showed that CME treatment substantially reversed the DOX-induced decrease in survival rate. Echocardiography indicated that CME treatment also reduced DOX-induced left ventricular systolic dysfunction, and a TUNEL assay showed that CME treatment also suppressed apoptosis in the mouse heart. These results reveal that CME treatment ameliorated DOX-induced cardiotoxicity by suppressing apoptosis. Further study is needed to clarify the effect of CME on DOX-induced heart failure in humans.