Żyro Dominik, Śliwińska Agnieszka, Szymczak-Pajor Izabela, Stręk Małgorzata, Ochocki Justyn
Departament of Bioinorganic Chemistry, Chair of Medicinal Chemistry, Medical University of Łódź, Muszyńskiego 1, 90-151 Łódź, Poland.
Department of Nucleic Acids Biochemistry, Medical University of Łódź, Pomorska 251, 92-213 Łódź, Poland.
Cancers (Basel). 2020 Dec 20;12(12):3848. doi: 10.3390/cancers12123848.
Antimicrobial properties of silver (I) ion and its complexes are well recognized. However, recent studies suggest that both silver (I) ion and its complexes possess anticancer activity associated with oxidative stress-induced apoptosis of various cancer cells. In this study, we aimed to investigate whether silver nitrate and its complexes with metronidazole and 4-hydroxymethylpyridine exert anticancer action against human pancreatic cancer cell lines (PANC-1 and 1.2B4). In the study, we compared decomposition speed for silver complexes under the influence of daylight and UV-A (ultraviolet-A) rays. We employed the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide) assay to evaluate the cytotoxicity and the alkaline comet assay to determine genotoxicity of silver nitrate and its complexes. Flow cytometry and the Annexin V-FITC/PI apoptosis detection kit were used to detect the apoptosis of human pancreatic cancer cells. We found a dose dependent decrease of both pancreatic cancer cell line viability after exposure to silver nitrate and its complexes. The flow cytometry analysis confirmed that cell death occurred mainly via apoptosis. We also documented that the studied compounds induced DNA damage. Metronidazole and 4-hydroxymethylpyridine alone did not significantly affect viability and level of DNA damage of pancreatic cancer cell lines. Complex compounds showed better stability than AgNO, which decomposed slower than when exposed to light. UV-A significantly influences the speed of silver salt decomposition reaction. To conclude, obtained data demonstrated that silver nitrate and its complexes exerted anticancer action against human pancreatic cancer cells.
银（I）离子及其配合物的抗菌特性已得到广泛认可。然而，最近的研究表明，银（I）离子及其配合物均具有抗癌活性，与氧化应激诱导的各种癌细胞凋亡相关。在本研究中，我们旨在探究硝酸银及其与甲硝唑和4-羟甲基吡啶形成的配合物是否对人胰腺癌细胞系（PANC-1和1.2B4）具有抗癌作用。在研究中，我们比较了日光和UV-A（紫外线-A）照射下银配合物的分解速度。我们采用MTT（3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐）法评估细胞毒性，并用碱性彗星试验测定硝酸银及其配合物的遗传毒性。使用流式细胞术和Annexin V-FITC/PI凋亡检测试剂盒检测人胰腺癌细胞的凋亡情况。我们发现，暴露于硝酸银及其配合物后，两种胰腺癌细胞系的活力均呈剂量依赖性下降。流式细胞术分析证实细胞死亡主要通过凋亡发生。我们还记录到所研究的化合物会诱导DNA损伤。单独的甲硝唑和4-羟甲基吡啶对胰腺癌细胞系的活力和DNA损伤水平没有显著影响。复合化合物显示出比AgNO更好的稳定性，AgNO在光照下分解得比复合化合物慢。UV-A显著影响银盐分解反应的速度。总之，所得数据表明硝酸银及其配合物对人胰腺癌细胞具有抗癌作用。
