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Information × Registration Number 0220U101195, 0117U000657 , R & D reports Title Investigation of the mechanisms of tumor growth inhibition through limiting of carbohydrate supply, inhibition of glycolysis and gluconeogenesis and induction of arginine starvation popup.stage_title Head Sybirnyi Andrii A., Registration Date 05-01-2020 Organization Institute of Cell Biology popup.description2 The effect of gluconeogenesis inhibitor metformin (MF) on the proliferative potential of human ovarian carcinoma SKOV3 and human hepatocarcinoma HepG2 cells was investigated. It was shown that the MF effect depends on the tissue origin of the cell line: HepG2 were more sensitive to metformin. The combined effect of arginine deficiency and glycolysis inhibitors 3-bromopyruvate (3-BrPr) and 2-deoxyglucose (2-DG) on the viability and proliferative potential of SKOV3 and HepG2 tumor cells has been studied. It was found that the effect of both 3-BrPr and its combination with MF under conditions of arginine deficiency was leveled by the transfer of cells to arginine-containing medium. The detected sensitivity to 2-DG monotherapy in the presence of arginine was cell-specific, and the combination with MF led to approximately threefold inhibition of growth in both lines tested. However, due to the lack of arginine, the cells of both lines were insensitive both to the effect of 2-DG and to the combination with 5 mM MF. After transfer to the arginine-containing medium, the effect of the inhibitors was not reflected in the growth characteristics of HepG2, whereas SKOV3 showed a slight decrease in proliferative parameters. Analysis of the effects of arginine deficiency and glycolysis or gluconeogenesis inhibitors on tumor cell signaling mechanisms revealed a slight increase in such effects as activation of the AMPK signaling pathway, blocking off the PI3K-AKT-mTOR, and cell cycle arrest. These changes did not lead to increased endoplasmic reticulum stress and were not stable, which, depending on the cellular origin, allowed more or less restore the functioning of key signaling pathways that ensure the proliferation of tumor cells after the termination of therapeutic effects. Keywords: human tumor cells, arginine starvation, inhibitors of glycolysis and gluconeogenesis, proliferative and metastatic potential, cell signaling. Product Description popup.authors Bobak Yaroslav P. Danyleychenko Valeriy V. Stasyk Oleh V. Chen Oleg I. Chernyshuk Svitlana V. popup.nrat_date 2020-04-02 Close