O2·- and NO-associated mechanisms of selective action of redox-active cobalt complexes on tumor tissue

Ganusevich I.I., Burlaka A.P.*, Sidorik E.P., Levitin I.Ya., Sigan A.L., Osinsky S.P.

Aim: To study the influence of redox-active cobalt(III) complex with tetradentate Schiff base and nicotinamide as an axial ligand on the rate of superoxide radical-anions generation and levels of NO in tumor and normal tissues of Lewis lung carcinoma bearing mice as well as activity of matrix metalloproteinases 2 and 9 (MMPs) in tumor. Methods: The superoxide radical-anions formation and NO level in tissues were assessed by EPR method with the use of 1-hydroxy-2,2,6,6-tetramethyl-4-oxopiperidin and diethyldithiocarbomate spin traps, respectively. MMPs activities were determined by zymography in polyacrylamide gel. Results: It was observed that the rate of superoxide radical-anions generation was selectively increased in tumor tissue (by a factor of 6–7) accompanied with the decrease of NO level (by a factor of 2) due to tested complex administration. Activities of MMPs in tumor were significantly decreased. Conclusion: It is supposed that the one of mechanisms of detected earlier antimetastatic effect of complex is based on its ability to induce the formation of high level of superoxide radical-anions selectively in the tumor tissue that results in the damage of its regulatory functions, in particular alteration in the regulation of NO-synthase, decrease of NO generation as well as activities of MMPs.

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