4.3 Article

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)

Journal

CELL BIOCHEMISTRY AND BIOPHYSICS
Volume 79, Issue 1, Pages 93-102

Publisher

HUMANA PRESS INC
DOI: 10.1007/s12013-020-00962-x

Keywords

Dinitrosyl iron complexes; Nitric oxide; Nitrosonium cations; Apoptosis

Funding

  1. Ministry of Education and Science [00008202014-0001b, AAAA-A17-117040610310-b, 0082-2014-0008, AAAA-A171170403100008-5]
  2. Russian Academic Excellence Project 5-100
  3. Russian Foundation for Basic Research [18-04-00059a]

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This study demonstrates that binuclear dinitrosyl iron complexes with thiol-containing ligands exhibit cytotoxic effects on MCF7 human breast cancer cells, mediated by nitrosonium cations released from these complexes. The cytotoxic effects are retained or even enhanced in the presence of N-Methyl-D-glucamine dithiocarbamate, supporting the release of NO+ cations from a [Fe(NO)(2)] fragment.
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)(2)] of B-DNIC-MS forming stable mononitrosyl complexes of iron with MGD and releasing NO+ cations from a [Fe(NO)(2)] fragment.

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