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ECPB 2019, 88(4): 63–72
Research articles

Ovarian cancer: Ca2+-dependent and Ca2+-independent isoforms of NO-synthase functioning in blood lymphocytes of women


The purpose of the work was to study the activity and kinetic parameters of isoforms of NO-synthase blood lymphocytes in women with ovarian cancer. Ovarian cancer is considered to be one of the most severe diseases of the female reproductive tract. The study of the pathogenesis of ovarian cancer is being directed to improve methods of diagnosis and detection of tumor formation process at an early stages. It is known that metabolism of L-arginine and synthesis of nitric oxide (NO) plays an important role in carcinogenesis and tumor growth. It is assumed that NO modulates cancer- dependent events, including angiogenesis, apoptosis, cell cycle, invasion and metastasis. The L-arginine is converted into NO by means of nitric oxide synthase (NOS) or ornithine with the participation of arginase, is carried out by separate metabolic pathways. According to physiological conditions, the NO production from L-arginine occurs by constitutive isoforms of NO-synthase (cNOS), which are Ca2+-dependent enzyme. The increase in NO production occurs as level of calcium ions increases. The stimulating factors of this receipts and, as a result, increase in calcium-dependent cNOS activity are acetylcholine, serotonin, glutamate, ADP and other biologically active substances. In pathophysiological conditions inflammatory stimuli induce the expression of the inducible isoform NO-synthase (iNOS), which is Ca2+-dependent isoform. One or more NOS isoforms exist in different human cells. These isoenzymes are expressed as expression products of different genes localized in separate chromosomes. Post-translational modification of these isoenzymes may affect their intracellular localization and activity. As for nitric oxide, according to various literary data, it plays a double role in processes of malignant growth. In high concentrations, it inhibits, and at low levels –stimulates tumor growth and metastasis. At the same time study the characteristics of changes in activity of individual isoforms of NOS during neoplastic transformation can be used as a basis for improving the quality of diagnosing and efficiency of this pathology correction. In order to recognize the pathological states of organism, peripheral blood lymphocytes can serve as one of the most appropriate model, which can objectively reflect changes in the genetic and metabolic homeostasis of organism and maladaptive states. This allows the use of metabolic parameters of lymphocytes as indicators of the functional state of organism. Studies were conducted on the blood lymphocytes of women with ovarian cancer of the degrees II-VI and healthy women (control group). It has been established that the activity of the constitutive isoform of NO-synthase lymphocytes in the blood of patients with cancer of the ovary goes down in 4.0 times in comparison with the control group.While the activity of the inducible isoform NO-synthase of blood lymphocytes in practically healthy women was identified to a small extent and was (1.52 ± 0.46) nmol NADPH(H+)∙min to 1 mg of protein. In ovarian cancer iNOS activity in blood lymphocytes increases 144 times. The maximum reaction rate for the constitutive isoform of the enzyme in cancer of ovary was reduced by 5 times, and for the inducible isoform grows in ten fold. For oncopathology the imaginary affinity constant inducible isoform of NO-synthase to arginine was in 5.4 times lower than that of constitutive isoforms of NO-synthase of blood lymphocytes of the control group and inhibition of constitutive isoform occurs by competitive type –by reducing the rate of enzyme turnover.

Received: 11.12.2019

Keywords: ovarian cancer, NO-synthase, lymphocytes, arginase, kinetic parameters

Full text: PDF (Ukr) 783K

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