Chrysanthemum morifolium Extract Ameliorates Doxorubicin-Induced Cardiotoxicity by Decreasing Apoptosis

被引：8

作者：

Ono, Masaya ^{[1
]}

Sunagawa, Yoichi ^{[1
,2
,3
]}

Mochizuki, Saho ^{[1
]}

Katagiri, Takahiro ^{[1
]}

Takai, Hidemichi ^{[1
]}

Iwashimizu, Sonoka ^{[1
]}

Inai, Kyoko ^{[1
]}

Funamoto, Masafumi ^{[1
,2
]}

Shimizu, Kana ^{[1
,2
]}

Shimizu, Satoshi ^{[1
,2
]}

Katanasaka, Yasufumi ^{[1
,2
,3
]}

Komiyama, Maki ^{[2
]}

Hawke, Philip ^{[4
]}

Hara, Hideo ^{[5
]}

Arakawa, Yoshiki ^{[6
]}

Mori, Kiyoshi ^{[3
,7
,8
]}

Asai, Akira ^{[9
]}

Hasegawa, Koji ^{[1
,2
]}

Morimoto, Tatsuya ^{[1
,2
,3
]}

机构：

[1] Univ Shizuoka, Sch Pharmaceut Sci, Div Mol Med, Shizuoka 4228526, Japan

[2] Natl Hosp Org, Div Translat Res, Clin Res Inst, Kyoto Med Ctr, Kyoto 6128555, Japan

[3] Shizuoka Prefectural Gen Hosp, Shizuoka 4208527, Japan

[4] Univ Shizuoka, Sch Pharmaceut Sci, Lab Sci English, Shizuoka 4228526, Japan

[5] UNIAL Co Ltd, Tokyo 1730005, Japan

[6] Kyoto Univ Grad Med, Dept Neurosurg, Kyoto 6068507, Japan

[7] Shizuoka Grad Univ Publ Hlth, Grad Sch Publ Hlth, Shizuoka 4200881, Japan

[8] Univ Shizuoka, Sch Pharmaceut Sci, Dept Mol & Clin Pharmacol, Shizuoka 4228526, Japan

[9] Univ Shizuoka, Ctr Drug Discovery, Grad Sch Pharmaceut Sci, Shizuoka 4228526, Japan

来源：

CANCERS | 2022年 / 14卷 / 03期

基金：

日本学术振兴会; 日本科学技术振兴机构;

关键词：

Chrysanthemum morifolium; doxorubicin; cardiomyopathy; apoptosis; p53; systolic dysfunction; CARDIAC MYOCYTE APOPTOSIS; HEART-FAILURE; CYTOTOXIC ACTIVITY; CANCER-TREATMENT; P300; THERAPY; COMPLICATIONS; HYPERTROPHY; FLAVONOIDS; TOXICITY;

D O I：

10.3390/cancers14030683

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. 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.

引用

页数：13

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