Chrysanthemum morifolium Extract Ameliorates Doxorubicin-Induced Cardiotoxicity by Decreasing Apoptosis

Cancers

Akira Asai¹  Yoshiki Arakawa²  Sonoka Iwashimizu³  Saho Mochizuki³  Masafumi Funamoto³  Satoshi Shimizu³  Yoichi Sunagawa³  Kyoko Inai³  Masaya Ono³  Hidemichi Takai³  Tatsuya Morimoto³  Takahiro Katagiri³  Koji Hasegawa³  Kana Shimizu³  Yasufumi Katanasaka³  Maki Komiyama⁴  Philip Hawke⁵  Kiyoshi Mori⁶  Hideo Hara⁷ 

[1] Center for Drug Discovery, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan;Department of Neurosurgery, Kyoto University Graduate of Medicine, Kyoto 606-8507, Japan;Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan;Division of Translational Research, Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan;Laboratory of Scientific English, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan;Shizuoka General Hospital, Shizuoka 420-8527, Japan;UNIAL Co., Ltd., Tokyo 173-0005, Japan;

关键词: Chrysanthemum morifolium;    doxorubicin;    cardiomyopathy;    apoptosis;    p53;    systolic dysfunction;   

DOI  :  10.3390/cancers14030683

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown