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Information × Registration Number 0221U100409, 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 V., Кандидат біологічних наук Registration Date 05-01-2021 Organization Institute of Cell Biology popup.description2  The influence of plant origin structural analogues of arginine, canavanine and indospicin, and modulators of both mTOR - signaling pathway and protein translation on the effectiveness of combined metabolic therapy based on arginine starvation of tumour cell was studied. For the first time, it was shown that indospicin selectively inhibits the viability of human colorectal cancer tumor cells under starvation of arginine by integrating into newly synthesized proteins, deregulating mTOR and MAPK signaling pathways, and causing endoplasmic reticulum (ER) stress and apoptosis. It has also been found that inactivation of pro-proliferative ERK and activation of proapoptotic p38 MARK may be one of the causes of antitumor effects of arginine analogues when arginine deprived. The significant role of c-Myc cancer protein level regulation, as well as MEK kinase inhibition in cell response to combinational therapy, has not been established. At the same time, the mTOR inhibitor rapamycin and the protein synthesis inhibitor cycloheximide showed cytoprotective effects under such conditions in colorectal cancer cells but had the opposite effect in human ovarian cancer cells. It was found that the simultaneous action of canavanine and the inhibitor of autophagy chloroquine significantly induces apoptotic death of ovarian carcinoma cells SKOV3. It has also been shown for the first time that constitutive activation of mTOR by knockout of the gene of mTOR repressor TSC2 increases the sensitivity of colorectal carcinoma SW480 cells to starvation for arginine, as well as sensitizes cells to the action of canavanine. The obtained results will be used to develop new approaches to combination therapy of tumors based on arginine starvation. Key words: human tumor cells, arginine starvation, structural analogues of arginine, modulators of mTOR - signaling pathway and protein translation, cell viability and survival, cell signaling pathways Product Description popup.authors Bobak Yaroslav P. Vovk Olena I Danyleichenko Valerii V Mayevska Oksana M Stasyk Oleh V Chen Oleg I Chernyshuk Svitlana V Shuvayeva Galina Yu popup.nrat_date 2021-01-05 Close