State Key Laboratory of Analytical Chemistry for Life Science and Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China.
Jiangsu Key Laboratory of Molecular Medicine, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, 210093, China.
Sci Rep. 2017 May 23;7(1):2296. doi: 10.1038/s41598-017-02510-9.
Better understanding the drug action within cells may extend our knowledge on drug action mechanisms and promote new drugs discovery. Herein, we studied the processes of drug induced chemical changes on proteins and nucleic acids in human breast adenocarcinoma (MCF-7) cells via time-resolved plasmonic-enhanced Raman spectroscopy (PERS) in combination with principal component analysis (PCA). Using three popular chemotherapy drugs (fluorouracil, cisplatin and camptothecin) as models, chemical changes during drug action process were clearly discriminated. Reaction kinetics related to protein denaturation, conformational modification, DNA damage and their associated biomolecular events were calculated. Through rate constants and reaction delay times, the different action modes of these drugs could be distinguished. These results may provide vital insights into understanding the chemical reactions associated with drug-cell interactions.
更好地理解药物在细胞内的作用机制可能会扩展我们对药物作用机制的认识，并促进新药的发现。在此，我们通过时间分辨等离子体增强拉曼光谱（PERS）结合主成分分析（PCA）研究了三种常用化疗药物（氟尿嘧啶、顺铂和喜树碱）在人乳腺癌（MCF-7）细胞中诱导蛋白质和核酸化学变化的过程。化学变化过程中，药物作用明显区分。计算了与蛋白质变性、构象修饰、DNA 损伤及其相关生物分子事件相关的反应动力学。通过速率常数和反应延迟时间，可以区分这些药物的不同作用模式。这些结果可能为理解与药物-细胞相互作用相关的化学反应提供重要的见解。
