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亚硝酰阳离子作为含巯基配体的二硝基金属配合物的细胞毒性成分(基于 MCF7 人乳腺癌细胞培养的实验工作)。

Nitrosonium Cation as a Cytotoxic Component of Dinitrosyl Iron Complexes with Thiol-containing Ligands (based on the Experimental Work on MCF7 Human Breast Cancer Cell Culture).

机构信息

Semenov Federal Research Centre of Chemical Physics, Russian Academy of Sciences, Moscow, Russia.

Institute of Regenerative Medicine, Sechenov Medical University, Moscow, Russia.

出版信息

Cell Biochem Biophys. 2021 Mar;79(1):93-102. doi: 10.1007/s12013-020-00962-x. Epub 2021 Jan 25.

Abstract

Here we demonstrate that binuclear dinitrosyl iron complexes with thiol-containing ligands (glutathione and mercaptosuccinate, B-DNIC-GSH and B-DNIC-MS, respectively) exert cytotoxic effects on MCF7 human breast cancer cells. We showed that they are mediated by nitrosonium cations released from these complexes (NO). This finding is supported by the cytotoxic effect of both B-DNICs on MCF7 cells evidenced to retain or was even promoted in the presence of N-Methyl-D-glucamine dithiocarbamate (MGD). MGD recruits an iron nitrosyl group [Fe(NO)] from the iron-dinitrosyl fragment [Fe(NO)] of B-DNIC-MS forming stable mononitrosyl complexes of iron with MGD and releasing NO cations from a [Fe(NO)] fragment.

摘要

在这里,我们证明了含有巯基配体(谷胱甘肽和巯基琥珀酸,分别为 B-DNIC-GSH 和 B-DNIC-MS)的双核二硝酰基铁配合物对 MCF7 人乳腺癌细胞具有细胞毒性作用。我们表明,这种作用是由这些配合物释放的亚硝酰阳离子(NO)介导的。这一发现得到了以下事实的支持:两种 B-DNIC 对 MCF7 细胞的细胞毒性作用都表明,在存在 N-甲基-D-葡糖胺二硫代氨基甲酸盐(MGD)的情况下,这种作用得以保留,甚至得到了促进。MGD 从 B-DNIC-MS 的铁-二硝酰基片段[Fe(NO)]中招募一个铁亚硝酰基[Fe(NO)],形成与 MGD 稳定的单核铁亚硝酰配合物,并从[Fe(NO)]片段释放 NO 阳离子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de0a/7829092/733995f00bed/12013_2020_962_Sch1_HTML.jpg

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