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Information × Registration Number 0217U000969, 0112U000614 , R & D reports Title Changes in expression of genes and activity of enzymes involved in carbohydrate and energy metabolism in malignant cells as mean of tumor growth suppression. popup.stage_title Head Sibirny Andriy Andrijovych, Registration Date 23-03-2017 Organization Institute of cell biology, National Academy of Sciences of Ukraine popup.description2 A comparative analysis of the impact of arginine, leucine, lysine and methionine deficiencies on gene expression induced by hypoxia in the models of tumor cells was conducted in our department. Under arginine lacking in cells of the head and neck cancers (SAS and FaDu) and coloncancer cells (HCT-116 and HT29) it was shown the expression of number genes of endoplasmic reticulum stress (ER), which are also involved in hypoxia cell response, such as VEGF, ATF4, CHOP, GRP78. Deficiency of leucine, lysine and methionine, respectively, led to similar changes in gene's expression. It was revealed that arginine depletion had no effect on expression of the HIF-1? transcription factor, but induced the accumulation of VEGF-A transcript in the analyzed cell lines, such as SAS, HCT-116 and HT29. Analysis of HCT-116 and HT29 multicellular spheroids, showed the increasing of the amount of HIF1? protein under arginine depletion in a spheroids with diameter of 400 ?m, which is a sign of hypoxia. In HT29 spheroids with sizes reaching to 650 ?m, the inhibition of mTOR and MAPK signaling pathways, development of ER stress and activation of the apoptosis were observed. We have not detected the impact of hypoxia inducer СоСl2 in concentrations of 0.1 and 0.2 mM on proliferation of HCT-116 and HT29 cells, incubated both in nutrient-rich and arginine-deficient conditions. It was studied the status of key regulators of energy balance in cells such as AMPK та S6 proteins, which are responsible for reduction of translation and stop the proliferation in tumor cells upon arginine deficiency. Usage the antidiabetic drug metformine, the AMPK inductor, resulted to activation of p38 MAPK, AMPK, S6 and stop the proliferation of cancer cells under nutrient-rich conditions but the cumulative effect on the viability of tumor cells using metformin upon arginine-depleted condition, we have not found. Product Description popup.authors Барська М.Л. Бобак Я.П. Вовк О.І. Карацай О.В. Курліщук Ю.В. Маєвська О.М. Сенчук О.Ю. Сибірна Н.О. Стасик О.В. Стасик О.Г. popup.nrat_date 2020-04-02 Close