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Introduction. Nitric oxide (NO) produced by NO synthases (NOS) is involved in the regulation of vital physiological functions. At the same time, NO and NOS are involved in events associated with the tumor process: mutagenesis, proliferation, apoptosis, angiogenesis, etc., exerting a multidirectional effect on the tumor.Objectives – analyze and summarize literature data concerning the role of NO and endothelial NOS (eNOS) in the initiation and progression of tumors, as well as in the inhibition of tumor growth.Materials and methods. In preparing the review, publications of information bases of biomedical literature were used: SciVerse Scopus (538), PubMed (1327), Web of Science (905), Russian Science Citation Index (125).Results. The molecular mechanisms of the action of NO and its derivatives on the initiation and progression of carcinogenesis have been explored. Numerous factors and conditions regulating the activity of eNOS in health and tumor growth have been analyzed. The molecular signaling pathways through which the pro-tumor effects of NO and eNOS, stimulating angiogenesis, lymphangiogenesis, are realized, including through the mobilization of stem cells, are considered.Conclusion. Nitric oxide produced by activated eNOS promotes tumor progression by increasing the proliferation of tumor cells, enhancing the action of pro-angiogenic factors, stimulating angiogenesis, lymphangiogenesis, and metastasis. Selective inhibition of increased eNOS activity may be a promising therapeutic approach aimed at reducing metastasis and tumor growth.

The review analyzes literature data and the results of our own research on the role of reactive nitrogen species (NO, NO 2 , N 2 O 3 ) in the initiation and progression of tumors. The possibility of modulating the activity of inducible NO synthase by the biologically active components of plant products and their effect on carcinogenesis is analyzed. Possible mechanisms of the ambiguous action of NO and its metabolic products in the mechanisms of carcinogenesis are discussed. The generalization and analysis of these data allowed us to formulate some principles for the use of substances that modulate the activity of inducible NO synthase and affect the formation of NO and its metabolic products in inhibiting carcinogenesis.

The dynamics of the production of nitric oxide (NO) metabolites: nitrites, nitrates, volatile nitrosamines and iNOS expression was studied in mice with subcutaneous transplanted, spontaneous and chemical- induced tumors. Tumor growth was accompanied by increased production of nitrites + nitrates in tumors or their release with urine that not dependent on tumor histotype. The total concentration of nitrites and nitrates in tumors reached micromolar levels characteristic of nitrosative stress. The ability of peritoneal macrophages + monocytes to generates nitrites was suppressed at the stage of intensive growth of the Lewis lung carcinoma, which may indicate a decrease in the cytotoxic properties of immune cells. The possibility of formation in the Erlich carcinoma of volative N-nitrosodimethylamine and N-nitrosodiethylamine compounds with pronounced carcinogenic properties was demonstrated. A positive expression of iNOS was revealed in some areas of lung carcinoma at all investigated time points using the immunohistochemical method. The lungs metastases were not stain or weakly stained. This may indicate selection of the cells with a low activity of iNOS migrating in the lungs.

The dynamics of the endogenous production of NO metabolites, nitrites, nitrates, and volatile nitrosamines, has been investigated in the body, a tumor tissue, and peritoneal macrophages of mice F1 (C57Bl × CBA), Balb/c and BDF with subcutaneously transplanted tumors: Ehrlich carcinoma (EC) and Lewis metastatic lung carcinoma (LC). It has been shown that during the first three weeks, growth of EC is accompanied by a statistically significant increase in the total concentration of NO metabolites (NOx; nitrites + nitrates) up to levels (7.3 ± 3.49) × 10−6−(7.8 ± 2.57) × 10−5 mol/kg in the tumor tissue and a sharp increase in NOx excretion with urine. At the same time, in the LC tumor tissue the maximal level of NOx (3.6 ± 0.46) × 10−5 mol/kg was registered on day 7, and later it decreased demonstrating negative correlation with the tumor mass. At the stage of intensive LC growth (14, 21 days) there was significant inhibition of nitrite secretion by peritoneal macrophages. In all the controlled time-intervals the EC tumor tissue contained carcinogenic N-nitrosodimethylamine and N-nitrosodiethylamine; however, their concentrations significantly varied. Thus, the ability of the tumor tissue to produce NO metabolites was more pronounced in EC than in LC and depended on the time parameters of tumor growth.

Administration of steroid glycosides of both the spirostanol type, where the active substance is deltonin, and the furostanol type, the main components of which are deltoside and protodioscine, before transplantation of Ehrlich carcinoma (EC) and during its growth had no effect on the body’s resistance to tumor cells, with no effect on the latent period of formation of tumor nodules or the rate of tumor growth. Testing in a therapeutic regimen demonstrated a tendency to stimulation of EC growth in response to spirostanol glycosides. At the same time, treatment with furostanol glycosides showed weak, statistically insignificant, inhibition of tumor growth, in terms of both tumor volume and tumor mass.

A comprehensive chemical study of the cultivated plant Allium schoenoprasum L. from the collection of the Botanical Garden of the Institute of Biology (Komi Scientific Center, UB, RAS) showed that its leaves contained a wide range of biologically active substances and trace elements involved in the antioxidant and anticarcinogenic protection system of humans. An experiment for the evaluation of the antitumor potential of these substances showed that the aqueous and aqueous-alcohol extracts of onion leaves tended to inhibit the growth of subcutaneously grafted Ehrlich carcinoma in male BDF mice at the stage of intense tumor development.

Oral treatment with lycopene (per os) in doses of 10 or 50 mg/kg for 2 weeks led to accumulation of lycopene in the liver, liver microsomes, and blood plasma, increased total plasma antioxidant activity, inhibited LPO in the liver, and decreased solubilization of lysosomal enzymes. Lycopene had no effect on ex vivo resistance of liver microsomes to LPO and activities of antioxidant enzymes in the liver.