Nitrosonium Cation as an Antitumor Component of Dinitrosyl Iron Complexes with Thiol-containing Ligands

Abstract

The combined use of two compounds, the binuclear form of dinitrozyl iron complexes with glutathione (100 µM/kg, subcutaneously) and sodium diethyldithiocarbamate (500 µM/kg, intraperitoneally), administered 8 times, caused complete inhibition of the development of a solid tumor in mice for 2 weeks after transplantation (Lewis lung carcinoma). However, when the antitumor effect was assessed on the 20th day after the end of drug administration, the maximum activity, inhibition of tumor growth by 60%, was observed when the drugs were administered in the sequence “diethyldithiocarbamate, and then 1 h later binuclear dinitrozyl iron complexes”; whereas when the drugs were used in the reverse sequence, inhibition of tumor growth did not exceed 30%. Based on the analysis of EPR measurements of tumor tissues (on the 15th day of tumor development), it was concluded that the inhibition of tumor growth was caused by nitrosonium cations released from binuclear dinitrosyl iron-glutathione complexes during the breakdown of these complexes under the action of sodium diethyldithiocarbamate.