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Information × Registration Number 0218U002544, 0117U004387 , R & D reports Title Development of methods for combined enzyme therapy and chemotherapy of malignantly transformed human cells using arginine-degrading enzymes popup.stage_title Head Stasyk Oleh Volodymyrovych, Кандидат біологічних наук Registration Date 10-04-2018 Organization Institute of cell biology, National Academy of Sciences of Ukraine popup.description2 The research to develop new methods of combinational enzyme therapy of human tumors based on arginine starvation and to find out the molecular causes and markers of sensitivity of tumor cells of different origins to such therapy was conducted. The obtained data indicate that arginine deficiency induces apoptosis in conditionally sensitive cells and adaptive mechanisms in conditionally resistant tumor cells that ensure survival of the latter under such conditions. It was shown that the effect of arginine fasting, mediated by such key signaling mechanisms as MAPK, AMPK, and mTOR, is prolonged and not alleviated within a few days after restoring the level of exogenous arginine. It was revealed that the combination of arginine starvation with low nontoxic dosages of canavanine (analogue of arginine), chloroquine (autophagy inhibitor) and nitric oxide donor (sodium nitroprusside) causes rapid loss of proliferative potential and death of SK-MEL-28 melanoma cells and SKOV3 ovarian carcinoma cells. It was showed that mTOR signaling activation with canavanine, and, consequently, the restoration of the translation in cells cultured in the nonarginine medium, promotes the active inclusion of canavanine in proteins, the accumulation of proteins with an abnormal structure, activation of endoplasmic reticulum stress and death of cancer cells through caspase-dependent apoptosis. It has been confirmed that the specific sensitivity of tumor cells to the combination of arginine deficiency and canavanine depends on the degree of inhibition of the total translation and the interaction of the GCN2 / eIF2alpha- and mTOR-dependent signaling pathways. Product Description popup.authors Бобак Я.П. Вовк О.І. Данилейченко В.В. Курліщук Ю.В. Маєвська О.М. Сибірна Н.О. Чень О.І. Чернишук С.В. Шуваєва Г.Ю. popup.nrat_date 2020-04-02 Close