Prooxidant and antioxidant processes in lymphoma cells under the action of pyrazolopyrimidine derivative

Abstract

Background. The influence in vitro of thiazole derivative 8-methyl-2-Me-7-[trifluoro­methyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]-thiazolo-[3,2-a]-pyrimidin-4(2H)-one (PP2) on the level of lipid peroxidation products, superoxide anion radical and antioxidant system activity in lymphoma cells was studied. A pronounced cytotoxic action of the thiazole derivative on the tumor cells in vitro was reported earlier, however, no cytotoxicity of this substance was detected toward non-cancerous cells. In addition, it was shown that the sca­vengers of active forms of Oxygen significantly reduced the cytotoxic effect of the studied compound. The purpose of this work was to investigate the effect of 8-methyl-2-Me-7-[trifluoromethyl-phenylmethyl]-pyrazolo-[4,3-e]-[1,3]-thiazolo-[3,2-a]-pyrimidin-4(2H)-one on the content of lipid peroxidation products, superoxide radical and the activity of enzymes of antioxidant defense in the lymphoma cells. Materials and Methods. Experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Ascites tumor cells were passaged by the intreperitoneal inoculation to mice. Abdominal drainage with ascites was performed with a sterile syringe under ether anesthesia. PP2 was dissolved in dimethylsulfoxide. The product content and enzymatic activity were determined spectrophotometrically. Statistical analysis of obtained results was carried out using MS Excel-2013 program. Results. The influence of the pyrazolopyrimidine derivative on the content of lipid peroxidation products and superoxide radical in lymphoma cells was investigated. It was found that the studied compound did not change the amount of the primary lipid peroxidation products, but reduced the amount of secondary products. A decrease in the MDA content under the action of the studied derivative indicates probable interaction of the substance with the reactive Oxygen species. Pyrazolopyrimidine derivative did not change the level of the superoxide radical. The effect of the thiazole derivative on the activity of key enzymes of the antioxidant system in lymphoma cells was investigated. The studied compound at the concentration of 10 µM activated superoxide dismutase. Pyrazolopyrimidine derivative decreased the activity of catalase and glutathione peroxidase. Such changes in the activity of enzymes can cause the growth of hydrogen peroxide in the cell, which is toxic in large quantities. Conclusions. The obtained results may indicate that the studied pyrazolopyrimidine derivative can realize its cytotoxic effect on lymphoma cells though the action on the pro­ducts of lipid peroxidation and antioxidant system activity. These data can be used to understand the mechanism of action of the studied compounds and for further improvement of their antitumor effect. Keywords: lymphoma, pyrazolopyrimidine derivative, lipid peroxidation, antioxidant system, antitumor drugs