Effect of a novel thiazole derivative and its complex with a polymeric carrier on stability of DNA in human breast cancer cells

Thiazole derivatives are perspective antitumor compounds characterized by a broad range of bioactivity, while polymeric carriers are widely used to enhance the efficiency of biological action of drugs, improve their biocompatibility and water solubility. Previously, we identified that the thiazole-based derivative BF1 (N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide) possessed differential toxicity towards targeted tumor cell lines. The aim of the present work was to investigate the action in vitro of BF1 and its complex with the polymeric carrier (PC) poly(PEGMA-co-DMM) (BF1-РС complex) towards human breast adenocarcinoma cells of the MDA-MB-231 and MCF-7 lines. DNA comet analysis, diphenylamine DNA fragmentation assay, gel retardation assay of plasmid DNA, DNA intercalation assay using methyl green dye and fluorescent microscopy were used to study the effects of BF1 on DNA stability in breast cancer cells. The ІС50 of cytotoxic action towards MDA-MB-231 cells was 26.5 ± 2.9 µМ for BF1, while the ІС50 for the BF1-PC complex was 6.9 ± 0.4 µМ, and the PC demonstrated low toxicity (ІС50 ˃ 50 µМ). The BF1-PC complex possessed higher toxicity towards MCF-7 cells than free BF1, with ІС50 of 9.6 ± 0.8 µМ and 15.8 ± 0.9 µМ, respectively. BF1 and BF1-PC induced an increase in the number of damaged cells of the MDA-MB-231 line with blebbing of plasma membrane, condensed chromatin and/or fragmented nucleus and micronuclei formation. Both BF1 and the BF1-PC complex induced single-strand breaks in DNA and its fragmentation in treated MDA-MB-231 cells. The studied compounds were not bound to plasmid DNA and did not intercalate into DNA molecules.