Comparison of cellular responses of parental and epirubicin-resistant non-small cell lung cancer cells against stabilized-ag ion solution induced injury

Abstract

Purpose: The aim of this study was to compare the responses of parental and epirubicin-resistant non-small cell lung cancer (NSCLC) cells against stabilized-silver (St-Ag) ion induced oxidative DNA and membrane injury after the cells treated with this solution. Material and Methods: IC50 values for parental and drug-resistant NSCLC cells as revealed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and resazurin-based assay. Malondialdehyde (MDA) levels in the cells were assayed by using fluorometric method. The genomic DNA samples were used to determine the amount of 8-hydroxy-2'-deoxyguanosine (8-OHdG) with a competitive ELISA kit.Results: 139 μg/mL for parental cells and 224 μg/mL for resistant cells were calculated as IC50 values by MTT assay. 96 μg/mL and 189 μg/mL respectively were calculated as IC50 values by resazurin-based assay. When the cells were treated with IC50 concentration of St-Ag ion solution, clear signs of oxidative stress, i.e. decreased is glutathione (GSH) (1.5-folds in parental, 2-folds in resistant) and glutathione peroxidase (GPx) (2-folds in parental), as well as increased lipid peroxidation (1.6-folds in parental, 2-folds in resistant) and 8-OHdG formation (1.5-folds in parental, 2-folds in resistant) were seen. Changes in the levels of glutathione-S-transferase (GST) in both cell type and levels GPx in resistant cells were statistically insignificant. The St-Ag ion solution has higher membrane and DNA damaging effect on resistant cells than parental cells even though resistant-cells have high GST and GPx activity. Conclusion: Thus our data suggest St-Ag ion solution has different potential toxicity on parental and epirubicin-resistant cancer cells depend on concentration that is associated with oxidative stress. Anticancer potential of anticancer drugs for especially drug resistant cells can be increased by combining therapy with stabilized-silver ion solution.