Generation of ROS under the influence of thiazole derivative and its complexes with PEG-based polymeric nanoparticles

Abstract

To determine the in vitro effect of thiazole derivative and its complex with polyethylene glycol (PEG)-based nanoscale particles on ROS generation in the NK/Ly lymphoma cells and hepatocytes of mice. Methods. The effects of BF-1 (N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide), PEG-based polymeric nanoparticles (Th1, Th3, Th5) and their complexes (Th2, Th4, Th6) on the ROS production in murine NK/Ly lymphoma cells were studied using fluorescent microscopy. The level of superoxide in both the murine hepatocytes and NK/Ly cells was determined with a spectrophotometric assay. Results. BF1, Th2, Th6 and Th5 significantly increased the level of ROS in NK/Ly lymphoma cells by 27.7 %, 28.6 % 22.7 % and 20.1 %, respectively. Meanwhile, Th1, Th3, Th4 did not affect the ROS level. The level of superoxide significantly decreased under the influence of BF1 by 14.7 % and all its complexes with PEG-based polymeric nanoparticles (Th2, Th4, Th6) by 25.5 %, 21.6 % and 13 %, respectively, compared to control. Unlike lymphocytes, in the murine hepatocytes none of the investigated compounds affected the superoxide content. Conclusions. Thus, thiazole derivative BF1 may realize its antitumor effect on cancer cells by promoting generation of additional amount of ROS. BF1 and its complexes with PEG-containing polymeric nanoparticles significantly increase the ROS generation in NK/Ly cells. Meanwhile, all investigated compounds did not change the level of superoxide in murine hepatocytes. It can be an evidence of their low toxicity to nontumor cells.

Activity of antioxidant enzymes in hepatocytes of mice with lymphoma under the action of thiazole derivative in complex with polymeric nanocarrier

“…It was previously established that thiazole derivative BF1 and its complexes with PNs significantly changed the activity of antioxidant enzymes in lymphoma cells [11]. In particular, the activity of SOD increased, while the activity of CAT and GPx decreased.…”

“…Previous studies have demonstrated that thiazole N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) possesses a significant level of toxicity towards some tumor cell lines, while exhibiting no destructive effects on pseudonormal cell lines and hepatocytes in NK/Ly mice [8,19]. The possible anticancer mechanism of action of the thiazole derivative based on the generation of a large number of ROS, which triggers a cascade of reactions in tumor cells that lead to their apoptosis [11].…”