Antitumor effect of OXY correlates with its ability to decrease the level of nitrosyl-hem complexes in lewis lung carcinoma cells

Boichuk I.V., Melnikov O.R., Solyanik G.I.

I. Boichuk, O. Melnikov, G. Solyanik

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv, Ukraine

Introduction: It is known that the tumor growth is accompanied by changes of redox carriers in the mitochondrial electron transport chain. These changes may result in decrease of energy metabolism. The functional state of the mitochondrial electron transport chain also defines the intensity of production and accumulation of the oxygen and nitrogen reactive species (ROS and NOS), which affect different biological processes and can promote cell damage. It has already been observed that non-cytotoxic doses of oxyresveratrol (OXY) showed significant antineoplastic and anti-metastatic effects and prolonged the life of animals with tumors. Aim: To analyze the influence of OXY on the mitochondrial iron-sulfur centers and nitrosyl-hem complexes of tumor cells during Lewis lung carcinoma growth. Materials and Methods: EPR method was used to analyze the OXY influence on the content of the mitochondrial iron-sulfur centers (g=1.94) and nitrosyl-hem complexes (g=2.007) in tumor tissues. The total dose of OXY was 0.2 mg/g of animal weight. The agent was administered per os from the 2nd day after cancer cell inoculation, 5 times/week, during 3 weeks. Tumor volume as well as characteristics of tumor mitochondrial electron transport chain was registered on the 10th, 14th, 16th, 20th, 25th day of the tumor growth. Results: It was shown that OXY affected the formation of nitrosyl-hem complexes in mitochondrial electron transport chain. In OXY free mice the level of nitrosyl-iron complexes was significantly increased during tumor growth, while the level of iron-sulfuric centers was progressively decreased. Treatment of LLC-bearing mice with OXY resulted in a considerable LLC growth inhibition and caused the reduction of NO-hem complexes. Its level at the end of the treatment (20th, day of tumor growth) was by 64% (р < 0.05) lower than that of control mice. In 5 days after therapy completion the level of NO-hem complexes in OXY treated mice was not changed compared to untreated animals. It was shown that OXY didn’t influence the content of iron-sulfuric centers in LLC. Conclusions: LLC growth is accompanied by decrease of iron-sulfur centers’ content and increase of nitrosyl-hem complexes in mitochondria of cancer cells. Decrease of the level of nitrosyl-hem complexes in cancer cells under OXY treatment correlates with an ability of OXY to inhibit LLC growth.

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