Majzner K, Wojcik T, Szafraniec E, Lukawska M, Oszczapowicz I, Chlopicki S, Baranska M
Faculty of Chemistry, Jagiellonian University, Ingardena 3, Krakow, Poland.
Analyst. 2015 Apr 7;140(7):2302-10. doi: 10.1039/c4an01882f.
Anthracycline antibiotics display genotoxic activity towards cancer cells but their clinical utility is limited by their cardiac and vascular toxicity. The aim of this study was to develop a Raman-based methodology to study the nuclear accumulation of anthracyclines in the endothelium. For this purpose bimodal confocal Raman and fluorescence imaging was used to monitor cellular composition changes as a result of anthracycline exposure on endothelial cells (EA.hy926), and nuclear drug accumulation, respectively. Simultaneously effects of anthracyclines on endothelium viability were investigated by caspases-3 and -7 and MTT assays. We demonstrated that nuclear accumulation of DOX and EDOX was similar; however, EDNR accumulated in endothelial nuclei at concentrations 10 times higher than DNR. In turn, epimers of DOX or DNR were both consistently less toxic on the endothelium as compared to their congeners as evidenced by MTT and caspase assays. In summary, bimodal Raman and fluorescence-based nucleus profiling proves to be a valuable tool to study structure-activity relationship of nuclear accumulation and toxicity of anthracyclines in endothelium.
蒽环类抗生素对癌细胞具有基因毒性活性，但其临床应用受到心脏和血管毒性的限制。本研究的目的是开发一种基于拉曼光谱的方法，以研究蒽环类抗生素在内皮细胞中的核积累情况。为此，采用双模态共聚焦拉曼光谱和荧光成像分别监测蒽环类抗生素暴露于内皮细胞（EA.hy926）后细胞成分的变化以及核药物积累情况。同时，通过半胱天冬酶-3和-7以及MTT实验研究蒽环类抗生素对内皮细胞活力的影响。我们证明多柔比星（DOX）和表柔比星（EDOX）的核积累情况相似；然而，表柔比星（EDNR）在内皮细胞核中的积累浓度比柔红霉素（DNR）高10倍。反过来，与它们的同系物相比，多柔比星（DOX）或柔红霉素（DNR）的差向异构体对内皮细胞的毒性始终较低，MTT实验和半胱天冬酶实验证明了这一点。总之，基于双模态拉曼光谱和荧光的细胞核分析被证明是研究蒽环类抗生素在内皮细胞中的核积累和毒性的构效关系的有价值工具。
