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Information × Registration Number 0224U000196, 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 03-01-2024 Organization Institute of Cell Biology of the National Academy of Sciences of Ukraine popup.description2 In the Department of Cell Signaling, research aimed at finding possible ways to increase the effectiveness of metabolic therapy based on arginine (Arg) starvation of human head and neck squamous cell carcinomas (HNSCC) in vitro in combination with an energy homeostasis modulator (3-bromopyruvate (3-BrPyr)) or a nucleoside antimetabolite - analogue of deoxycytidine (gemcitabine (GEM)) have conducted. The metastatic potential of FaDu (human pharyngeal carcinoma) and SAS (human tongue carcinoma) cell lines was analyzed using several appropriate analytical methods. In particular, the IC50 for 3-BrPyr and GEM was determined both under the conditions of complete medium and under Arg deficiency; optimally selected concentrations of the studied factors used to assess the viability and proliferative potential of malignant cells; the influence of the compounds mentioned above on cell signalling controlled motility, adhesive and invasive properties, namely the FAK-PI3K-Akt signalling cascade, was investigated. It was shown that GEM increases the effectiveness of combination therapy based on Arg deprivation. In particular, the combination of Arg starvation and GEM impaired the ability of tumour cells to resume proliferation after incubation under Arg deficiency for several days. For the first time, it was shown the additive effect of the energy metabolism inhibitor 3-BrPyr on the survival and proliferative potential of FaDu and SAS tumor cells as well as the deregulation of several cell signalling pathways in the absence of Arg. At the same time, 3-BrPyr did not significantly affect the adhesive properties. However, a significant decrease in the level of activation of FAK-kinase, but not of the AKT-dependent pathway, was noted in the cells. Thus, it is possible to recommend GEM and 3-BrPyr as factors that prevent the recovery of HNSCC proliferation in combination or after the effect of metabolic therapy. Product Description popup.authors Bobak Yaroslav P. Olena I. Vovk Danyleichenko Valerii Vasyl'ovych Demash Dmytro Valeriyovych Polishchuk Nikita Valentynovych Stasyk Olena Georgiivna Chernyshuk Svitlana V Shuvayeva Galina Yuriivna popup.nrat_date 2024-01-03 Close