Effect of a novel thiazole derivative and its complexes with polymeric carriers on the processes of lipid peroxidation in lymphoma cells

Abstract

Background. Many types of tumors are sensitive to changes in prooxidant-antioxidant balance. Thus, further studies on reactive oxygen species inducing antitumor drugs that generate oxidative stress-dependent cytotoxic effects are promising. Our previous works showed that thiazole derivatives in combination with polymeric carriers have a pronounced cytotoxic effect on tumor, while not being cytotoxic against pseudo-normal cells in vitro. It was found that thiazole derivatives in complex with PEG-based polymeric carriers affected the antioxidant system of lymphoma cells in vitro. The aim of this work was to study the in vitro effect of the complex of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) in combination with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th1), poly(PEGMA) (Th3) and poly(PEGMA-co-DMM) (Th5) on the level of lipid peroxidation products in NK/Ly cells. Materials and Methods. The experiments were conducted on white wild-type male mice with a grafted NK/Ly lymphoma. Ascites tumor cells were inoculated into mice intraperitoneally. Abdominal drainage with ascites of anesthetized mice was performed with a sterile syringe on the 7th–10th days after inoculation. Investigated compounds BF1, polymeric carriers Th1, Th3, Th5 and combination of BF1 + Th1 (Th2), BF1 + Th3 (Th4) and BF1 + Th5 (Th6) at a final concentration of 10 μM were added to the lymphoma samples and incubated for 10 minutes. The level of lipid peroxidation products, such as lipid hydroperoxides and thiobarbituric acid-positive products) were determined according to the techniques described below. Results. All applied complexes based on thiazole derivative BF1 and PEG-based polymeric carriers at a concentration of 10 μM increased the activity of lipid hydroperoxi­des in the lymphoma cells by 29–36% compared to control. Complexes Th2 and Th6 increased the significance of BF1 influence on lymphoma cells from P <0.05 to P <0.01. Among all of the studied complexes, Th4 and Th6 significantly increased the level of TBA-positive products, while Th2 and BF1 did not change the content of the secondary products of lipid peroxidation. None of the unconjugated polymeric carriers affected the level of lipid peroxidation products. Conclusions. Thus, based on the results of this work, thiazole derivative BF1 in complex with polymeric carriers increases the level of primary and secondary products of lipid peroxidation in lymphoma cells. Polymeric carriers enhanced the effect of thiazole derivative on the studied parameters, so complexes of thiazole derivatives and PEG-containing polymeric carriers should be taken into consideration and further investigated as potential antitumor agents.