Bioenergetic characteristics of the murine Nemeth-Kellner lymphoma cells exposed to thiazole derivative in complex with polymeric nanoparticles

M. Ilkiv, Ya. R. Shalai, H. Mazur, B. O. Manko, B. V. Manko, Y. Ostapiuk, N. Mitina, A. Zaichenko, A. Babsky
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Abstract

The development of a new anticancer drugs targeted at energy metabolism of tumor cells is a promising­ approach for cancer treatment. The aim of our study was to investigate the action of thiazole derivative N-(5-benzyl-1,3-thiazol-2-yl)-3,5-dimethyl-1-benzofuran-2-carboxamide (BF1) and its complex with PEG based polymeric nanoparticle (PEG-PN) on respiration and mitochondrial membrane potential in murine NK/Ly tumor cells. The rate of oxygen uptake in NK/Ly cells was recorded by a polarographic method using a Clark electrode. The mitochondrial potential relative values were registered using fluorescence TMRM dye. No changes in glucose-fuelled basal respiration or maximal FCCP-stimulated respiration was detected after 15-min incubation of cells with BF1 (10 µM), PEG-PN or BF1 + PEG-PN complex Fluorescent microscopy data showed that BF1 or PEG-PN separately had no effect on the value of mitochondrial membrane potential, while BF1 + PEG-PN complex caused a significant decrease in mitochondrial membrane potential, indicating­ on the decrease of NK/Ly cells viability. Keywords: cell respiration, mitochondrial membrane potential, NK/Ly tumor cells, PEG, polymeric nanoparticles, thiazole derivative
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噻唑衍生物与聚合物纳米颗粒复合物暴露于小鼠Nemeth-Kellner淋巴瘤细胞的生物能量特性
以肿瘤细胞的能量代谢为靶点的新型抗癌药物的开发是一种很有前途的癌症治疗方法。本研究旨在研究噻唑衍生物N-(5-苄基-1,3-噻唑-2-基)-3,5-二甲基-1-苯并呋喃-2-羧酰胺(BF1)及其与PEG基聚合物纳米颗粒(PEG- pn)配合物对小鼠NK/Ly肿瘤细胞呼吸和线粒体膜电位的作用。用Clark电极极谱法记录NK/Ly细胞的摄氧速率。用荧光TMRM染料记录线粒体电位相对值。细胞与BF1(10µM)、PEG-PN或BF1 + PEG-PN复合物孵育15 min后,葡萄糖驱动的基础呼吸和fccp刺激的最大呼吸均无变化。荧光显微镜数据显示,BF1或PEG-PN单独对线粒体膜电位值无影响,而BF1 + PEG-PN复合物导致线粒体膜电位显著降低,表明NK/Ly细胞活力降低。关键词:细胞呼吸,线粒体膜电位,NK/Ly肿瘤细胞,聚乙二醇,纳米聚合物,噻唑衍生物
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