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

Exp Oncol. 2007 Sep;29(3):203-6.

Abstract

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.

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / drug therapy*
  • Carcinoma, Lewis Lung / metabolism*
  • Cobalt / pharmacology*
  • Female
  • Matrix Metalloproteinase 2 / drug effects
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / drug effects
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / analysis
  • Nitric Oxide / metabolism*
  • Oxidation-Reduction
  • Spin Trapping
  • Superoxides / analysis
  • Superoxides / metabolism*

Substances

  • Superoxides
  • Nitric Oxide
  • Cobalt
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9