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首页> 外文期刊>Metabolites >1 H HR-MAS NMR-Based Metabolomics of Cancer Cells in Response to Treatment with the Diruthenium Trithiolato Complex [( p -MeC 6 H 4 i Pr) 2 Ru 2 (SC 6 H 4 - p -Bu t ) 3 ] + (DiRu-1)
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1 H HR-MAS NMR-Based Metabolomics of Cancer Cells in Response to Treatment with the Diruthenium Trithiolato Complex [( p -MeC 6 H 4 i Pr) 2 Ru 2 (SC 6 H 4 - p -Bu t ) 3 ] + (DiRu-1)

机译：1 H HR-MAS基于NMR的癌细胞代谢组学与三硫合钌络合物[（p -MeC 6 H 4 i Pr）2 Ru 2（SC 6 H 4-p -Bu t）3]响应] +（ DiRu-1）

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The trithiolato bridged diruthenium complex DiRu-1 [( p -MeC 6 H 4 i Pr) 2 Ru 2 (SC 6 H 4 - p -Bu t ) 3 ] + is highly cytotoxic against various cancer cell lines, but its exact mode of action remains unknown. The present 1 H HR-MAS NMR-based metabolomic study was performed on ovarian cancer cell line A2780, on its cis-Pt resistant variant A2780cisR, and on the cell line HEK-293 treated with 0.03 μM and 0.015 μM of DiRu-1 corresponding to full and half IC 50 doses, respectively, to investigate the mode of action of this ruthenium complex. The resulting changes in the metabolic profile of the cell lines were studied using HR-MAS NMR of cell lysates and a subsequent statistical analysis. We show that DiRu-1 in a 0.03 μM dose has significant impact on the levels of a number of metabolites, such as glutamine, glutamate, glutathione, cysteine, lipid, creatine, lactate, and acetate, especially pronounced in the A2780cisR cell line. The IC 50 /2 dose shows some significant changes, but full IC 50 appears to be necessary to observe the full effect. Overall, the metabolic changes observed suggest that redox homeostasis, the Warburg effect, and the lipid metabolism are affected by DiRu-1.
机译：Trithiolato桥联的钌络合物DiRu-1 [（p -MeC 6 H 4 i Pr）2 Ru 2（SC 6 H 4-p -Bu t）3] +对多种癌细胞系具有高度细胞毒性，但其确切模式为行动仍然未知。当前的基于1 H HR-MAS NMR的代谢组学研究是在卵巢癌细胞系A2780，其顺铂耐药变体A2780cisR和用0.03μM和0.015μMDiRu-1处理的HEK-293细胞系上进行的分别以50和50次IC 50剂量研究这种钌配合物的作用方式。使用细胞裂解物的HR-MAS NMR和随后的统计分析研究了细胞系代谢谱中所得的变化。我们显示0.03μM剂量的DiRu-1对许多代谢物的水平具有显着影响，例如谷氨酰胺，谷氨酸，谷胱甘肽，半胱氨酸，脂质，肌酸，乳酸盐和乙酸盐，在A2780cisR细胞系中尤其明显。 IC 50/2剂量显示出一些显着变化，但要观察到完整的效果，似乎需要完整的IC 50。总体而言，观察到的代谢变化表明DiRu-1影响氧化还原稳态，Warburg效应和脂质代谢。

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