https://scholars.lib.ntu.edu.tw/handle/123456789/531985
標題: | Baicalein protects against doxorubicin-induced cardiotoxicity by attenuation of mitochondrial oxidant injury and JNK activation | 作者: | WEI-TIEN CHANG Li J. Haung H.-H. Liu H. Han M. Ramachandran S. Li C.-Q. Sharp W.W. Hamann K.J. Yuan C.-S. Hoek T.L.V. Shao Z.-H. |
公開日期: | 2011 | 卷: | 112 | 期: | 10 | 起(迄)頁: | 2873-2881 | 來源出版物: | Journal of Cellular Biochemistry | 摘要: | The cardiotoxicity of doxorubicin limits its clinical use in the treatment of a variety of malignancies. Previous studies suggest that doxorubicin- associated cardiotoxicity is mediated by reactive oxygen species (ROS)-induced apoptosis. We therefore investigated if baicalein, a natural antioxidant component of Scutellaria baicalensis, could attenuate ROS generation and cell death induced by doxorubicin. Using an established chick cardiomyocyte model, doxorubicin (10μM) increased cell death in a concentration- and time-dependent manner. ROS generation was increased in a dose-response fashion and associated with loss of mitochondrial membrane potential. Doxorubicin also augmented DNA fragmentation and increased the phosphorylation of ROS-sensitive pro-apoptotic kinase c-Jun N-terminal kinase (JNK). Adjunct treatment of baicalein (25μM) and doxorubicin for 24h significantly reduced both ROS generation (587±89a.u. vs. 932a.u.±121a.u., P<0.01) and cell death (30.6±5.1% vs. 46.8±8.3%, P<0.01). The dissipated mitochondrial potential and increased DNA fragmentation were also ameliorated. Along with the reduction of ROS and apoptosis, baicalein attenuated phosphorylation of JNK induced by doxorubicin (1.7±0.3 vs. 3.0±0.4-fold, P<0.05). Co-treatment of cardiomyocytes with doxorubicin and JNK inhibitor SP600125 (10μM; 24h) reduced JNK phosphorylation and enhanced cell survival, suggesting that the baicalein protection against doxorubicin cardiotoxicity was mediated by JNK activation. Importantly, concurrent baicalein treatment did not interfere with the anti-proliferative effects of doxorubicin in human breast cancer MCF-7 cells. In conclusion, baicalein adjunct treatment confers anti-apoptotic protection against doxorubicin-induced cardiotoxicity without compromising its anti-cancer efficacy. Copyright ? 2011 Wiley-Liss, Inc. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/531985 | ISSN: | 0730-2312 | DOI: | 10.1002/jcb.23201 | SDG/關鍵字: | anthra[1,9 cd]pyrazol 6(2h) one; baicalein; doxorubicin; lactate dehydrogenase; reactive oxygen metabolite; stress activated protein kinase; animal cell; apoptosis; article; cancer cell; cardiotoxicity; cell death; cell proliferation; cell survival; chick; DNA fragmentation; heart muscle cell; human; human cell; mitochondrial membrane potential; mitochondrial respiration; nonhuman; phosphorylation; priority journal; DNA Fragmentation; Doxorubicin; Enzyme Activation; Flavanones; JNK Mitogen-Activated Protein Kinases; Membrane Potential, Mitochondrial; Myocytes, Cardiac; Phosphorylation; Reactive Oxygen Species; Scutellaria baicalensis; Scutellaria baicalensis |
顯示於: | 醫學院附設醫院 (臺大醫院) |
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