Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives

Finiuk, Nataliya; Ivasechko, Iryna; Klyuchivska, Olga; Ostapiuk, Yu. V.

doi:10.15407/ubj91.02.029

Cited by 10 publications

(14 citation statements)

References 24 publications

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“…In our previous studies, we found that the novel thiazole derivatives BF1 and PP2 activate caspasedependent and mitochondria-associated mechanism of apoptosis [6,7]. In order to reveal potential morphological changes in mitochondria in NK/Ly lymphoma cells under treatment with BF1 and PP2, we have carried out the electron microscopy study of these cells.…”

Section: Discussionmentioning

confidence: 99%

“…These compounds also had low toxicity towards human kidney cells (HEK 293) and human keratinocytes (HaCaT line) [5,8]. Previously we have identified that BF1 increased the level of Bax and Bim pro-apoptotic proteins in glioma cells [6], and PP2 increased the level of pro-apoptotic Bim protein and the mitochondriaspecific EndoG nuclease, and decreased the level of the anti-apoptotic Bcl-2 protein in the leukemia cells in vitro [7].…”

mentioning

confidence: 96%

“…introduction Thiazole derivatives are attractive heterocycles for pharmaceutical and medicinal chemists who design new potent anticancer agents [1][2][3][4]. It was shown that two novel thiazole derivatives -N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) and 7-benzyl-8-methyl-2-propylpyrazolo[4,3-e]thiazolo [3,2-a] pyrimidin-4(2H)-one (PP2) [5] have a high cytotoxic effect toward various cancer cell lines, such as glioblastoma (U251 and T98G) and human myeloid leukemia (HL 60 and K562) [6,7]. These compounds also had low toxicity towards human kidney cells (HEK 293) and human keratinocytes (HaCaT line) [5,8].…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 99%

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confidence: 96%

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confidence: 99%

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

Hreniukh¹,

Finiuk²,

Shalai³

2020

Ukr.Biochem.J.

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“…electrophoretic gel retardation assay of plasmid DNa. Plasmid DNA (1 μg) pEGFPc-1 (Clontech, Mountain View, California, USA) was mixed with 2 μl of MI-1 (1; 10; 100 μg/ml), and Dox (1 and 10 μg/ml) in 18 µl of 0.9% sodium chloride (Arterium, Lviv, Ukraine) at room temperature for 1 h. Prepared mixture was analyzed by electrophoresis in 1% agarose gel (Lachema, Brno, Czech Republic) with 1× Tris acetate (TAE) buffer containing 1 μg/ ml of Ethydium bromide (Sigma-Aldrich, St. Louis, Missouri, USA) for approximately 1 h at a constant voltage of 70 V. The trans-illuminator (MacroVue UV-20, Hoeffer, Troy, Michigan, USA) was used for visualization of plasmid DNA [21].…”

Section: Methodsmentioning

confidence: 99%

Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA

Finiuk¹,

Ivasechko²,

Klyuchivska³

et al. 2020

Ukr.Biochem.J

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“…Afterwards, 200 µL of the colored solution was transferred into a 96-well plate. The percentage of DNA fragmentation was calculated as {OD tube B / (OD tube A + OD tube B) × 100 %} [2,11]. The optical density (OD) was measured at 630 nm using Absorbance Reader BioTek ELx800 (BioTek Instruments, Inc., Winooski, Vermont, USA).…”

Section: Methodsmentioning

confidence: 99%

Inhibitor of protein kinases 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione induces DNA damage and apoptosis in human colon carcinoma cells

Finiuk¹,

Klyuchivska²,

Kuznietsova³

et al. 2020

Biol. Stud.

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Background. The heterocyclic scaffolds are in the list of key structural blocks used at synthesis of novel biologically active compounds. Materials and Methods. The present study addressed the evaluation of the mechanisms of the DNA damaging and pro-apoptotic actions in vitro of the maleimide derivative 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione (MI-1) targeting human colon carcinoma cells of HCT116 line. The Western-blot analysis was used to study changes in apoptosis-associated proteins, DNA comet assay under alkaline conditions was applied for evaluation of the DNA-damaging events, and Barton’s assay with diphenylamine was applied for measuring the level of DNA fragmentation in human colon carcinoma cells treated with MI-1 compound. Results. The results of the Western-blot analysis demonstrated that MI-1 induced the apoptosis in HCT116 cells via mitochondria-dependent pathway. It activated caspase 3 via its cleavage in the treated human colon carcinoma cells. Besides, MI-1 increased the content of mitochondria-specific proteins: endonuclease G (EndoG) and the pro-apoptotic cytosolic protein protease-activating factor 1 (Apaf1). At the same time, MI-1 reduced the level of the anti-apoptotic Bcl-2 protein in HCT116 cells. The DNA comet analysis under alkaline conditions of the targeted human colon carcinoma cells of HCT116 line demonstrated that MI-1 induced DNA single-strand breaks in line with the olive tail moment of 13.2. The results of the colorimetric diphenylamine assay in HCT116 cells have shown that cell treatment with MI-1 increased the content of fragmented DNA to 14.2 %. Conclusions. The anti-proliferative action of MI-1 in human colon carcinoma cells of HCT116 line is associated with apoptosis induction via mitochondria-dependent pathway, as well as the DNA damage through single-strand breaks and DNA fragmentation. These data suggest that the 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione (MI-1) might be a promising agent for suppression of growth of colon tumor cells. Keywords: 1Н-pyrrole-2,5-diones, apoptosis, Western-blot assay, comet assay, single-strand breaks, Barton’s assay, DNA fragmentation

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Apoptosis induction in human leukemia cells by novel 2-amino-5-benzylthiazole derivatives

Cited by 10 publications

References 24 publications

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

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

Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA

Inhibitor of protein kinases 1-(4-chlorobenzyl)-3-chloro-4-(3-trifluoromethylphenylamino)-1Н-pyrrole-2,5-dione induces DNA damage and apoptosis in human colon carcinoma cells

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