Department of Applied Science, National Hsinchu University of Education, Hsinchu, Taiwan.
J Biomed Sci. 2013 Dec 20;20(1):95. doi: 10.1186/1423-0127-20-95.
Cancer has continually been the leading cause of death worldwide for decades. Thus, scientists have actively devoted themselves to studying cancer therapeutics. Doxorubicin is an efficient drug used in cancer therapy, but also produces reactive oxygen species (ROS) that induce severe cytotoxicity against heart cells. Quercetin, a plant-derived flavonoid, has been proven to contain potent antioxidant and anti-inflammatory properties. Thus, this in vitro study investigated whether quercetin can decrease doxorubicin-induced cytotoxicity and promote cell repair systems in cardiomyocyte H9C2 cells.
Proteomic analysis and a cell biology assay were performed to investigate the quercetin-induced responses. Our data demonstrated that quercetin treatment protects the cardiomyocytes in a doxorubicin-induced heart damage model. Quercetin significantly facilitated cell survival by inhibiting cell apoptosis and maintaining cell morphology by rearranging the cytoskeleton. Additionally, 2D-DIGE combined with MALDI-TOF MS analysis indicated that quercetin might stimulate cardiomyocytes to repair damage after treating doxorubicin by modulating metabolic activation, protein folding and cytoskeleton rearrangement.
Based on a review of the literature, this study is the first to report detailed protective mechanisms for the action of quercetin against doxorubicin-induced cardiomyocyte toxicity based on in-depth cell biology and proteomic analysis.
几十年来,癌症一直是全球范围内导致死亡的主要原因。因此,科学家们一直积极致力于癌症治疗学的研究。阿霉素是一种用于癌症治疗的有效药物,但也会产生活性氧(ROS),对心肌细胞造成严重的细胞毒性。槲皮素是一种植物来源的类黄酮,已被证明具有强大的抗氧化和抗炎特性。因此,这项体外研究调查了槲皮素是否可以降低阿霉素诱导的细胞毒性并促进心肌细胞 H9C2 中的细胞修复系统。
进行了蛋白质组学分析和细胞生物学测定,以研究槲皮素诱导的反应。我们的数据表明,槲皮素处理可在阿霉素诱导的心脏损伤模型中保护心肌细胞。槲皮素通过抑制细胞凋亡和通过重新排列细胞骨架来维持细胞形态,显著促进细胞存活。此外,2D-DIGE 结合 MALDI-TOF MS 分析表明,槲皮素可能通过调节代谢激活、蛋白质折叠和细胞骨架重排来刺激心肌细胞在阿霉素处理后修复损伤。
根据文献综述,本研究首次基于深入的细胞生物学和蛋白质组学分析,报道了槲皮素对抗阿霉素诱导的心肌细胞毒性的作用的详细保护机制。