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


CONCLUSIONS
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.
Ganusevich
I I
II
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kiev, Ukraine.
Burlaka
A P
AP
Sidorik
E P
EP
Levitin
I Ya
IY
Sigan
A L
AL
Osinsky
S P
SP
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology*; D005260:Female; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D010084:Oxidation-Reduction; D019097:Spin Trapping; D013481:Superoxides / Q000032:analysis / Q000378:metabolism*
D013481:Superoxides; D009569:Nitric Oxide; D003035:Cobalt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9