Jabłońska-Trypuć Agata, Świderski Grzegorz, Krętowski Rafał, Lewandowski Włodzimierz
Division of Sanitary Biology and Biotechnology, Faculty of Civil Engineering and Environmental Engineering, Białystok University of Technology, Wiejska 45E Street, Białystok 15-351, Poland.
Division of Chemistry, Bialystok University of Technology, Białystok 15-351, Poland.
Molecules. 2017 Jul 4;22(7):1106. doi: 10.3390/molecules22071106.
Doxorubicin (DOX) is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different mechanism of action has arisen. The aim of the present study was to evaluate the influence of newly synthesized DOX complexes with selected metals (Mg, Mn, Co, Ni, Fe, Cu, Zn) on apoptosis, cell cycle, viability, proliferation and cytotoxicity in the breast cancer cell line MCF-7. Complexation of DOX with metals has likewise been the subject of our research. The current work showed that the tested bivalent metals at a given pH condition formed metal:DOX complexes in a ratio of 2:1, while iron complexes with DOX in a ratio of 3:1. The studies also showed that selected metal-DOX complexes (Mg-DOX, Mn-DOX, Ni-DOX) at 0.5 µM concentration significantly decreased cell viability and proliferation, however they increased caspase 7 activity. Results also indicated that studied metal-DOX complexes showed high cytotoxicity in MCF-7 cells. Therefore they were chosen for cell cycle check-points and apoptosis/necrosis analysis studied by flow cytometry. Obtained results suggest that doxorubicin complexed by specified metals can be considered as a potential anti-breast cancer agent, which is characterized by a higher efficacy than a parent drug.
阿霉素（DOX）是一种非常有效的化疗药物，然而它有几个主要缺点。因此，开发具有不同作用机制的新型抗癌药物复合物的动机应运而生。本研究的目的是评估新合成的DOX与选定金属（镁、锰、钴、镍、铁、铜、锌）形成的复合物对乳腺癌细胞系MCF-7的凋亡、细胞周期、活力、增殖和细胞毒性的影响。DOX与金属的络合同样也是我们的研究课题。目前的工作表明，在给定的pH条件下，所测试的二价金属与DOX形成的金属：DOX复合物的比例为2:1，而铁与DOX形成的复合物比例为3:1。研究还表明，浓度为0.5µM的选定金属-DOX复合物（镁-DOX、锰-DOX、镍-DOX）显著降低了细胞活力和增殖，但它们增加了半胱天冬酶7的活性。结果还表明，所研究的金属-DOX复合物在MCF-7细胞中显示出高细胞毒性。因此，它们被选用于通过流式细胞术进行细胞周期检查点和凋亡/坏死分析。获得的结果表明，特定金属络合的阿霉素可被视为一种潜在的抗乳腺癌药物，其特点是比母体药物具有更高的疗效。
