Curcumin potentiates doxorubicin-induced apoptosis in H9c2 cardiac muscle cells through generation of reactive oxygen species
Curcumin potentiates doxorubicin-induced apoptosis in H9c2 cardiac muscle cells through generation of reactive oxygen species
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DOI：
10.1016/j.fct.2011.01.021
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发表时间：
2011-05-01
影响因子：
4.3
通讯作者：
Karimi, Gholamreza
中科院分区：
文献类型：
--
作者：
Hosseinzadeh, Leila;Behravan, Javad;Karimi, Gholamreza
多柔比星（DOX）是一种广泛使用的化疗药物。DOX治疗癌症患者的主要不良反应是心肌病和心力衰竭的发作。活性氧（ROS）被认为是DOX心脏毒性的原因。姜黄素是从姜黄中提取的天然化合物，以其抗氧化特性而闻名。它已被确定为增加细胞凋亡的几种癌细胞系与阿霉素的组合，但很少有关于姜黄素和阿霉素对正常心肌细胞的影响的研究。因此，我们评估了姜黄素对DOX诱导的心肌细胞凋亡的影响。姜黄素预处理可通过下调Bcl-2、上调caspase-8和caspase-9的表达，增加阿霉素诱导的心肌细胞凋亡。姜黄素预处理1h后Bax/Bcl-2比值显著升高。此外，姜黄素通过DOX增加ROS生成。作为对DOX的反应，NF-κ B被激活。然而，姜黄素能够抑制NF-κ B活化。总之，我们的研究结果表明，用无毒浓度的姜黄素预处理通过产生ROS使H9 c2细胞对DOX介导的凋亡敏感。(C)2011爱思唯尔有限公司保留所有权利。
Doxorubicin (DOX) is a widely used chemotherapy agent. The major adverse effect of DOX treatment in cancer patients is the onset of cardiomyopathy and heart failure. Reactive oxygen species (ROS) are proposed to be responsible for DOX cardiotoxicity. Curcumin, a natural compound extracted from Curcuma Longa L., is known for its anti-oxidant properties. It has been identified as increased apoptosis in several cancer cell lines in combination with doxorubicin, but there are few studies about the effect of curcumin and doxorubicin on normal cardiac cells. Therefore, we evaluated the effects of curcumin on apoptosis induced by DOX in cardiac muscle cells. Preteatment with curcumin significantly increased DOX-induced apoptosis of cardiac muscle cells through down regulation of Bcl-2, up-regulation of caspase-8 and caspase-9. The Bax/Bcl-2 ratio increased significantly after 1 h pretreatment with curcumin. As well, curcumin increases ROS generation by DOX. In response to DOX, NF-kappa B was activated. However, curcumin was able to inhibit NF-kappa B activation. In conclusion, our results indicated that pretreatment with nontoxic concentrations of curcumin sensitized H9c2 cells to DOX-mediated apoptosis by generation of ROS. (C) 2011 Elsevier Ltd. All rights reserved.