The Antitumor Properties of Dinitrosyl Iron Complexes with Thiol-Containing Ligands and S-Nitrosoglutathione in Experiments

Abstract—The antitumor activity of S-nitrosoglutathione, bi- and mononuclear dinitrosyl iron complexes with different thiol-containing ligands such as glutathione, mercaptosuccinate, and thiosulfate was studied in models of transplantable murine solid tumors (Lewis lung carcinoma, Acatol adenocarcinoma, and Ca-755 adenocarcinoma). The highest antitumor activity, that is, 90% inhibition of tumor cell growth, was shown by the preparations of dinitrosyl iron complexes with glutathione via intravenous injection (Lewis lung carcinoma) and S-nitrosoglutathione via intraperitoneal injection (Ca-755 adenocarcinoma) to animals. Considering these results together with previous data on the antitumor activity of this type of compound, as well as the results of other researchers in this field, we hypothesized that the antitumor effect is mainly caused by the ability of these compounds to act as donors of nitrosonium ions. Nitrosonium ion-induced S-nitrosation of thiol-containing proteins on the surface of tumor cells leads to an increase in the intracellular oxidative capacity, thus promoting apoptosis and death of tumor cells.