Effect of novel 2-amino-5-benzylthiazole derivative on cellular ultrastructure and activity of antioxidant system in murine lymphoma cells

Shalai, Ya. R.; Popovych, M. V.; Kulachkovskyy, O. R.; Hreniukh, V. P.; Mandzynets, S. М.; Finiuk, Nataliya; Babsky, Andriy M.

doi:10.30970/sbi.1301.591

Cited by 6 publications

(9 citation statements)

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“…The action of the substance led to a deformation of the plasma membrane and nucleus, and to a decrease in the nucleus/ cytoplasmic ratio. These changes are similar to the effect of thiasole derivative (PP2) when lymphoma cells were incubated with the chemical in vitro [14]. We believe that these morphological changes are the result of apoptosis-like perturbations, such as an activation of poly (ADP-ribose) polymerase 1 and caspase 3 cleavage, as well as an increase in the level of pro-apoptotic Bim protein and the mitochondrion-specific EndoG nuclease, and a decrease in the level of the anti-apoptotic Bcl-2 protein [3].…”

Section: Resultssupporting

confidence: 59%

“…PP2 complexed with polymeric carriers at concentration of 10 µM caused changes of apoptotic type in the ultrastructure of lymphoma cells. Earlier, it was shown that 2-amino-5-benzylthiazole derivative caused necrosis in lymphoma cells in vitro [14]. In this study, necrotic changes in the ultrastructure under the action of the studied substances were not observed, while signs of apoptotic changes were detected.…”

Section: Resultscontrasting

confidence: 42%

“…Thiazole derivatives also caused DNA single-strand breaks and DNA fragmentation in leukemia cells [2]. We have shown that antiproliferative action of PP2 may be related to a violation of the activity of some enzymes of the antioxidant system (catalase, glutathione-peroxidase) [14].…”

Section: Resultsmentioning

confidence: 90%

“…It was found that these derivatives cause cytotoxic effects on some lines of tumor cells associated with a lipid peroxidation and superoxide radicals in vitro [13]. As has been previously reported, thiazole derivatives inhibit cancer cell growth and proliferation through a variety of mechanisms, leading to apoptosis or/and necrosis of tumor cells [2,3,14].…”

Section: Introductionmentioning

confidence: 76%

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Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo

et al. 2021

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Background. A pronounced cytotoxic action of the thiazole derivatives complexed with polymeric carriers on tumor cells in vitro was reported earlier, while no cytotoxicity of these compounds was detected toward noncancerous cells. It was found that thiazole derivatives at concentrations of 10 and 50 µM affected lymphoma cell ultrastructure in vitro. The purpose of this work was to investigate the effect 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) and its complexes with polymeric carriers poly(VEP-co-GMA)-graft-mPEG (Th12) and poly(PEGMA) (Th14) on the ultrastructure of lymphoma cells in vivo. Materials and Methods. Experiments were conducted on white wild-type male mice with grafted NK/Ly lymphoma. Ascite tumors were created by intreperitoneal inoculation of 1–2 mln of Nemet–Kelner lymphoma cells to mice. On the 12th day after inoculation, the body weight of animals was increased by 140–160 % mostly due to ascites growth. For treatment of ascites three solutions of the chemical compounds were prepared: PP2, PP2 + Th12, PP2 + Th14 and administered to the mice intraperitoneally for 5 days. The final concentration of PP2 was 5 mg/kg of body weight. Abdominal drainage from ascites was performed with a sterile syringe under chloroform anesthesia on the 10th day after the start of treatment. The ultrastructure of the cells was examined by electron microscopy. Results. Еlectron microscopy study showed that control lymphoma cells have a special subcellular formations such as a relatively large nucleus, and specific plasma membrane filaments. The effects of thiazole derivative revealed apoptotic and necrotic manifestations of cytotoxicity, such as a deformation and disintegration of nucleus, a decreased nucleus/cytoplasm ratio, a destruction of the plasma membrane and a change of mitochondria shape. The studied compound complexed with polymeric carriers caused an apoptotic-like changes in lymphoma cells. Under the action of such complexes, the nucleus/cytoplasm ratio decreased and the area of mitochondria increased. Conclusions. The obtained results suggest that the tested compounds induce apoptosis in tumor cells. Complexes of thiazole derivative with polymers do not impair the effect of the compound on lymphoma cells. The obtained data can be used to carry out further preclinical studies of thiazole derivatives complexed with polymeric carriers as potential antitumor drugs.

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Section: Resultssupporting

confidence: 59%

Section: Resultscontrasting

confidence: 42%

Section: Resultsmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 76%

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Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo

et al. 2021

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“…Mitochondria play an important role in cellular metabolism, including production of reactive oxygen species (ROS). It was shown that the studied compounds activate superoxide dismutase and decrease the activity of catalase and glutathione peroxidase doi: https://doi.org/10.15407/ubj92.02.121 [9]. These effects may lead to accumulation of H 2 O 2 in lymphoma cells, which can be toxic for cancer cells.…”

mentioning

confidence: 99%

Effects of thiazole derivatives on intracellular structure and functions in murine lymphoma cells

Hreniukh¹,

Finiuk²,

Shalai³

2020

Ukr.Biochem.J.

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of treated NK/Ly cells and their mitochondria was examined using electron microscopy. The rate of oxygen uptake by isolated mitochondria was recorded by a polarographic method using a Clark electrode. The mitochondrial potential relative values were registered using fluorescence dye rhodamine 123. In the short-term (15 min), incubation with BF1 and PP2 in 10 and 50 µM concentrations induced apoptotic and necrotic changes in the structure of NK/Ly cells, such as fragmentation and disintegration of the nucleus, destruction of the plasma membrane, and an increase in numbers of lysosomes and mitochondria. a polarographic method did not show significant metabolic shifts in lymphoma mitochondria, in either in vitro or ex vivo actions of the thiazole derivatives. However, fluorescent microscopy showed a significant decrease in mitochondria potential, following a 15 min incubation of cells with 50 µM of PP2. Thus, the electron and fluorescent microscopy data suggest that mitochondria are involved in the mechanism of cytotoxic action of the studied thiazole derivatives.

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

Finiuk¹,

Klyuchivska²,

Ivasechko³

et al. 2021

Ukr.Biochem.J

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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 ІС 50 of cytotoxic action towards MDA-MB-231 cells was 26.5 ± 2.9 µМ for BF1, while the ІС 50 for the BF1-PC complex was 6.9 ± 0.4 µМ, and the PC demonstrated low toxicity (ІС 50 ˃ 50 µМ). The BF1-PC complex possessed higher toxicity towards MCF-7 cells than free BF1, with ІС 50 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.

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Effect of novel 2-amino-5-benzylthiazole derivative on cellular ultrastructure and activity of antioxidant system in murine lymphoma cells

Cited by 6 publications

References 7 publications

Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo

Effect of thiazole derivative complexed with nanoscale polymeric carriers on cellular ultrastructure of murine lymphoma cells in vivo

Effects of thiazole derivatives on intracellular structure and functions in murine lymphoma cells

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

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