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Information × Registration Number 0217U000857, 0113U000141 , R & D reports Title The study of molecular mechanisms in response of tumor cells to the action of enzymotherapy based on starvation for arginine popup.stage_title Head Stasyk Oleh Volodymyrovych, Кандидат біологічних наук Registration Date 10-03-2017 Organization Institute of cell biology, National Academy of Sciences of Ukraine popup.description2 The study of the effect of arginine deprivation on proteins and cytoskeleton functions in tumor cells was carried out in the Department of Cell Signaling. It was revealed that cell lines of melanomas (SK-Mel 28 and WM793) and gliomas (U251, U87) in response on arginine deficiency acquire significant specific changes in morphology (reduction in cell sizes, altered form of lamellipodia, the lack of long filopodias, the loss of intensive coloring of actin in the apical ends of the cells) and the reorganization of actin microfilaments (shown by lowered fluorescence of the F-actin, which is associated with a reduction in actin polymerization), causing a significant drop in migration and invasiveness of tumor cells. Arginine deprivation also led to tubulin depolymerization, the main component of microtubules, in investigated tumor cells. The changes of the studied parameters of the cytoskeleton and mobility of tumor cells depended only on the lack of arginine, since in the absence of lysine such changes were not observed. The effect of arginine deficiency on the activity of the individual components of the MAPK and PI3K/Akt/mTOR signaling pathways was analyzed. It was shown that the dynamics of Akt1 phosphorylation (activation) and changes of phosphorylation (activation) of p38 MAPK in the cells of melanomas and gliomas under arginine absence were similar (amount of phosphorylated form of the corresponding proteins increased the most at the first day of incubation in arginine-free medium). Under the same experimental conditions we detected changes in phosphorylation of ribosomal protein S6, but these changes had a specific pattern, depending on the type of the cell line. In both cell lines (U251 glioma and melanoma WM793) S6 phosphorylation level decreased within 12 h of arginine-free incubation. However, although the amount of the phosphorylated protein S6 in U251 cells remained minimal for the experiment, the melanoma WM793 cells displayed the reactivation of S6 on 24 hour. The level of ERK1/2 phosphorylation depended on cell line^ sharply decreased in glioma cells but largely remained unchanged in melanoma cells. It was shown that under arginine withdrawal the exogenous donor of arginine nitric oxide in low physiological concentrations (0.1 mM) reduces the ability to restore cell growth, enhances apoptosis and reduces the invasiveness and clonogenic potential, of melanoma cells, but not their motility. We suggested that the appropriate combinational therapy comprising arginine-degrading enzyme and exogenous donor of nitric oxide may be used in the clinics to reduce the toxic effects associated with deficiency of nitric oxide in the body under arginine limitation. Product Description popup.authors Ігуменцева Н.І. Барська М.Л. Бобак Я.П. Вовк О.І. Воробець З.Д. Данилейченко В.В. Карацай О.В. Курліщук Ю.В. Маєвська О.М. Переверзєва Г.Г. Сенчук О.Ю. Сибірна Н.О. Стасик О.Г. Чернишук С.В. Шуваєва Г.Ю. popup.nrat_date 2020-04-02 Close