Antitumour Activity of Dinitrosyl Iron Complexes with Thiol-Containing Ligands in Animals: An Overview

Abstract

The data reviewed herein strongly suggest that binuclear dinitrosyl iron complexes (DNIC) with glutathione can fully (by 100%) suppress the growth of rapidly proliferating nonmalignant endometrial tumours in rats with experimental endometriosis, on the one hand, and retard the growth of transplanted malignant solid tumours (Lewis lung carcinoma), on the other hand. An inverse correlation was established between the antitumour effect of DNIC with glutathione on Lewis carcinoma and the mode of DNIC administration (intraperitoneal or intravenous). In the former case, the maximum inhibition of tumour growth was achieved by treatment of animals with the highest (200µmoles/kg) dose of DNIC, while after intravenous administration the inhibiting effect of DNIC increased with a decrease of the drug dose to 2µmoles/kg. It was suggested that Lewis carcinoma cells respond to DNIC used as a nitric monoxide (NO) donor by the development of a system of antinitrosative protection similar to that formed in many bacterial species in response to treatment with NO or its derivatives. It is not excluded that DNIC with thiol-containing ligands can fully suppress tumour growth when used as a nitrosonium (NO+) ion (but not NO) donor, as could be evidenced from the results of recent studies by Prof. Liaw et al. [Inorg. Chem. 2016, 55, 9383].