Ono Masaya, Sunagawa Yoichi, Mochizuki Saho, Katagiri Takahiro, Takai Hidemichi, Iwashimizu Sonoka, Inai Kyoko, Funamoto Masafumi, Shimizu Kana, Shimizu Satoshi, Katanasaka Yasufumi, Komiyama Maki, Hawke Philip, Hara Hideo, Arakawa Yoshiki, Mori Kiyoshi, Asai Akira, Hasegawa Koji, Morimoto Tatsuya
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.
Cancers (Basel). 2022 Jan 28;14(3):683. doi: 10.3390/cancers14030683.
It is well known that the anthracycline anticancer drug doxorubicin (DOX) induces cardiotoxicity. Recently, 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.
众所周知，蒽环类抗癌药物阿霉素（DOX）会诱发心脏毒性。最近，紫菊花提取物（CME）已被报道具有多种生理活性，如抗氧化和抗炎作用。然而，其对DOX诱导的心脏毒性的影响仍不清楚。一种3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）检测显示，1 mg/mL的CME可降低DOX对H9C2细胞的细胞毒性，但对MDA-MB-231细胞无此作用。一项TUNEL检测表明，CME处理可改善DOX诱导的H9C2细胞凋亡。此外，CME处理可显著抑制DOX诱导的p53、磷酸化p53和裂解的caspase-3、9表达水平升高。接下来，我们研究了CME在体内的作用。结果表明，CME处理可显著逆转DOX诱导的存活率下降。超声心动图显示，CME处理还可减轻DOX诱导的左心室收缩功能障碍，TUNEL检测表明，CME处理也可抑制小鼠心脏的凋亡。这些结果表明，CME处理通过抑制凋亡改善了DOX诱导的心脏毒性。需要进一步研究以阐明CME对人类DOX诱导的心力衰竭的影响。
