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首页> 外文期刊>Journal of cellular biochemistry. >A Novel Danshensu Derivative Prevents Cardiac Dysfunction and Improves the Chemotherapeutic Efficacy of Doxorubicin in Breast Cancer Cells
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A Novel Danshensu Derivative Prevents Cardiac Dysfunction and Improves the Chemotherapeutic Efficacy of Doxorubicin in Breast Cancer Cells

机译：新型丹参素衍生物可预防心脏功能异常并提高阿霉素在乳腺癌细胞中的化学治疗功效

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摘要

Doxorubicin (Dox) is an anthracycline antibiotic widely used in clinics as an anticancer agent. However, the use of Dox is limited by its cardiotoxicity. We have previously shown that a Danshensu (DSS) derivative, ADTM, displayed strong cardioprotective effects. With improved chemical stability and activity, a novel DSS derivative, D006, based on the structure of ADTM, was synthesized. In the present study, the protective effects of D006, indexed by attenuation of the cardiotoxicity induced by Dox as well as chemosensitizing effects that increase the antitumor activity of Dox, were investigated. Our results showed that D006 was more potent than either parental compound, or their use in combination, in ameliorating Dox-induced toxicity in H9c2 cells. In our zebrafish model, D006, but not DSS, alone significantly preserved the ventricular function of zebrafish after Dox treatment. Moreover, D006 upregulated mitochondrial biogenesis and increased mtDNA copy number after Dox treatment of H9c2 cells. D006 promoted the expression of HO-1 protein in a time-dependent manner while the HO-1 inhibitor, Znpp, reversed the protective effects of D006. Inhuman breast tumor MCF-7 cells, D006 enhanced Dox-induced cytotoxicity by increasing apoptosis. In conclusion, our results indicate that a new DSS derivative exhibits promising protective effects against Dox-induced cardiotoxicity both in vivo and in vitro, an effect at least partially mediated by induction of HO-1 expression and the activation of mitochondrial biogenesis. Meanwhile, D006 also potentiated the anti-cancer effects of Dox in breast tumor cells. (C) 2015 Wiley Periodicals, Inc.
机译：阿霉素（Dox）是一种蒽环类抗生素，在临床上广泛用作抗癌剂。但是，Dox的使用受到其心脏毒性的限制。先前我们已经表明，丹参素（DSS）衍生物ADTM具有很强的心脏保护作用。具有改进的化学稳定性和活性，基于ADTM的结构，合成了新的DSS衍生物D006。在本研究中，研究了D006的保护作用，该作用以Dox诱导的心脏毒性的减弱为指标，还研究了增加Dox抗肿瘤活性的化学增敏作用。我们的结果表明，D006在减轻Dox诱导的H9c2细胞毒性方面比母体化合物或其组合更有效。在我们的斑马鱼模型中，D006处理后，仅D006而不是DSS显着保留了斑马鱼的心室功能。此外，D006在Dox处理H9c2细胞后上调线粒体生物发生并增加mtDNA拷贝数。 D006以时间依赖性方式促进HO-1蛋白的表达，而HO-1抑制剂Znpp逆转D006的保护作用。在人类乳腺肿瘤MCF-7细胞中，D006通过增加细胞凋亡来增强Dox诱导的细胞毒性。总之，我们的结果表明，新的DSS衍生物在体内和体外均表现出对Dox诱导的心脏毒性的有希望的保护作用，这种作用至少部分地由HO-1表达的诱导和线粒体生物发生的激活介导。同时，D006还增强了Dox对乳腺癌细胞的抗癌作用。 （C）2015威利期刊公司

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