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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 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.

The aim of the present study was to investigate the dynamics of nitric oxide derivative (NOD) formation in mice with transplanted tumors and to analize whether synthetic NO-synthase inhibitors, NO-donors and natural compounds could modulate NOD synthesis.In the study F(1)(C(57)BlxCBA), CBA/Lac, BDF and Balb/c mice were used. Endogenous NOD synthesis in mice with transplanted Ehrlich carcinoma (EC) and Lewis lung carcinoma (LLC) was estimated by measuring urine nitrates (NA) and nitrites (NI) excretion and their concentration in tumor tissue determined by cadmium-reduction method.It is shown that EC development is accompanied by increased endogenous NOD formation whereas LLC growth - by its decrease. Total NOD excretion with urine in EC-bearing mice during tumor development was in the range of 1.1x10(-7)-7.0x10(-6) mol/kg body weight that was 1.7-6.8 times higher than that in LLC-bearing mice. Treatment of EC-bearing animals with N(ώ)-nitro-L-arginine and aminoguanidine resulted in decreased NOD formation causing moderate tumor growth retardation. Effect of treatment with nitroprusside was shown to be dependent on the rout of its administration and dosage. Treatment of EC-bearing mice with picnogenol, tannic acid, spirulina and paprika enriched with selenium resulted in tumor growth inhibition at the early stage of EC growth accompanied by stimulation of endogenous NOD formation.Regulation of endogenous NOD formation towards normal physiological levels or hyperproduction of these compounds may result in tumor growth suppression.

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.

The inhibiting effect of organic Se (selen-enriched yeast Bioselen) on the endogenous synthesis of N-nitrosubstances was investigated in the Wistar rats, receiving 15 mg of sodium nitritis and 24 mg of diethylamin per 1 kg of bodyweight during 22 days. The level of nitrosoprolin synthesis and (NPro) and the level of nitrosodiethyl (NDie) in the stomach of rats served as the main indices. The highest level of NPro and NDie were revealed in the rats, without selen supplementation (581.2 +/- 113.3 mg per kg of bodyweight and 29.8 +/- 3.0 mg per kg of bodyweight). The highest inhibiting effect of Se was 54.5% for NPro and 54.7% for NDie and it was shown for the Se concentration of 1.5 mg per 1 kg of forage. The increase of Se dosage to 3.0 mg per 1 kg of forage was less effective and resulted in 25.5% of inhibiting of NPro u 47.0% - NDie.