Poster
# 33
Poster |
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6th Internet World Congress for Biomedical Sciences |
Sergej P. Osinsky, M.D.,(1), I Levitin(2), L Bubnovskaya(3), A Sigan(4), I. Ganusevich(5), V. Michailenko(6), T. Kovelskaya(7)
(1)(2)(3)(4)(5)(6)(7)Inst. exp. Pathol. Oncol. Radiobiol. - Kiev . Ukraine
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[Biophysics] |
[Oncology] |
The interaction of metal complexes with biological systems, which is the field of biocoordination chemistry, draws increasing interest. Some authors have shown the anticancer activity of a number of cobalt-containing compounds in vitro and in vivo (1,3-7). These data suggest that further investigations with cobalt complexes are warranted. The novel cobalt(III) complexes have been designed in our laboratories.
These complexes contain, besides a tetradentate Schiff ligand, certain biogenic and hence physiologically active Lewis bases (8). Such "inorganic" cobalt(III) complexes (that are containing no metal-carbon bond) can be reduced in tumor, due to the reductive nature of many tumors which contain significant regions at low oxygen tensions. Thus they initiate a catalytic autooxidation process involving generation of reactive oxygen species. The coordinated biogenic ligands may reduce toxic side effects caused by xenobiotic core of these complexes, contribute to their antitumor action and facilitate their transport through cell membranes. Above mentioned results have shown that "inorganic" cobalt(III)- Schiff base complexes display significant antitumor, in particular antimetastatic, and thermoradiomodifying activities in vivo with rodent tumors.
The working hypothesis to explain the above mentioned effects of cobalt complexes is based on the suggestion that the partial reduction products of dioxygen, in the presence of transition metal complexes yield very reactive species, which could start catalytic oxidation of substrates and show antitumor action. The study of detailed mechanisms of biological activity of our cobalt(III) complexes are under way. Some preliminary results are presented below.
Our investigations have shown that malonyldialdehyde concentration was increased by a factor of 3,5 in tumor to the 60th min after AC-30 injection, in liver and kidney - 1,5 and 2, respectively. Glutathione (GSH) content was decreased by a factor of 2 in tumor, at the same time, in liver and kidney - by 10% and by a factor of 3, respectively. Glutathione-S-transferase activity was decreased by a factor of 2 in tumor, in liver and kidney - by 10 and 20%, respectively. Decreased both GSH content and GST activity in tumor were kept unchanged within 24 h. All indices in normal tissues were reached the pretreatment values to the 24 h. These data confirm the suggestion that our complexes are selectively reduced in tumor with the following initiation of catalytic autooxidation process involving generation of reactive oxygen species. This oxidative stress activated the peroxidation of lipid and other biomolecules with the formation of MDA and definite response of gluthatione´s system. It was observed by 31P-NMR spectroscopy that the ratio of nucleotide/inorganic phosphate and phosphocreatine/inorganic phosphate in tumor tissue fell by 76 and 90% respectively within 2 h of AC-30 complex administration and remained constant for a further 4 h. The ratio of these metabolites in muscle fell by 25 and 32% within 2 h of treatment. These results indicated that cobalt complex selectively and significantly decreased the bioenergetic status of the tumor.
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[Biophysics] |
[Oncology] |
