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Information × Registration Number 0223U000088, 0122U002256 , R & D reports Title Development of new selective approaches to metabolic antitumor therapy based on recombinant human arginase and cellular stress modulators popup.stage_title Head Stasyk Oleh V., Доктор біологічних наук Registration Date 03-01-2023 Organization Institute of Cell Biology of the National Academy of Sciences of Ukraine popup.description2 The Department of Cell Signaling conducted in vitro research on the models of human head and neck tumor cells to find possible ways to increase the effectiveness of metabolic therapy based on arginine starvation. It was shown that curcumin, the plant-derived AMPK inducer, did not have a significant cytotoxic effect on head and neck cancer FaDu cells in an arginine-deficient medium, but had a significant negative impact on the residual proliferative potential of these cells. It was also established that the simultaneous action of curcumin and the arginine analogue canavanine under arginine deficiency led to a dramatic inhibition of the MAPK (ERK1/2) signaling pathway. Under the combined arginine starvation and gemcitabine, a nucleoside antimetabolite and analogue of deoxycytidine, the cumulative effect was not observed. It was previously revealed increased gene expression of some heteromeric amino acid transporters, including SLC3A2 (CD98) and SLC7A5 (LAT1), in head and neck cancer (HNSCC) tumors compared to normal tissues, as well as a negative correlation between high expression of these genes and survival of patients with HNSCC. It was found that in human tongue carcinoma cells of the Cal-33 line, arginine deficiency led to complete growth arrest and their ability to restore growth was retained even after long-term starvation of this amino acid. Cal-33 cells were shown to have high levels of CD98 and LAT1 proteins, but CRISPR-Cas9-mediated knockout of the amino acid transporter gene SLC3A2 (CD98) did not sensitize these cells to arginine, leucine, or methionine deficiency. The obtained results will be used to improve the combined therapy of tumors based on amino acid starvation. Keywords: human tumor cells, arginine starvation, modulators of energy homeostasis, arginine analogues, amino acid transporter CD98-LAT1, proliferative potential, signaling pathways.  Product Description popup.authors Bobak Yaroslav P. Vovk Olena I Hruba Olena Ivanivna Danyleichenko Valerii Vasyl'ovych Demash Dmytro Valeriyovych Stasyk Olena Georgiivna Chen Oleg I Chernyshuk Svitlana V Shuvayeva Galina Yuriivna popup.nrat_date 2023-01-03 Close