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Information × Registration Number 0225U001103, (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 Аналіз впливу дефіциту аргініну та розроблених терапевтичних комбінацій на основі рекомбінантної аргінази-І людини на експресію позаклітинних (асоційованих із плазматичною мембраною чи секреторних) форм HSP білків. Аналіз впливу інгібування відповідних білків у комбінації з рекомбінантною аргіназою-І на життєздатність, проліферативний та клоногенний потенціал пухлинних клітин Head Stasyk Oleh V., Доктор біологічних наук Registration Date 25-01-2025 Organization Institute of Cell Biology of the National Academy of Sciences of Ukraine popup.description1 The aim of this work is to develop and analyze new combined approaches to antitumor metabolic therapy based on recombinant human arginase and cellular stress inducers, including analogues of arginine (canavanine, indospicin), analogues of pyrimidine bases, and energy metabolism modulators. Also, the work's goal is the identification of new molecular markers of human tumor cell sensitivity to appropriate therapy to develop more effective and selective approaches and predict the effectiveness of their application to different types of tumors popup.description2  The Department of Cell Signaling Mechanisms conducted studies aimed at increasing the effectiveness of metabolic cancer therapy based on arginine and other individual amino acid starvation. It was shown that endoplasmic reticulum (ER) stress and heat shock proteins (HSPs) play an important role in the response of malignant cells to arginine starvation or its combination with chemotherapeutic factors. I n particular, it was established in various cell models of malignant tumors that the level of ER stress determines the level of caspase-dependent apoptosis in the cell, and chaperone proteins counteract ER stress and play a protective role. We have established that certain heat shock proteins (in particular, HSP70 and HSP90) are subject to induction by arginine starvation and by the action of arginine analogue, canavanine, in human glioma cells. Also, the expression level of these proteins increases with repeated adaptation of head and neck cancer cells (SAS-R9 cell line) to the action of recombinant human arginase (or arginine deficiency). At the same time, the role of individual proteins (e.g. HSPB8) or their isoforms remains poorly understood and requires further research. It has been shown for the first time that an increase in the level of HSPs can be induced by oxidative stress factors, in particular low doses of doxorubicin. It has been shown that in human intestinal carcinoma cells HCT-116, the level of the chaperone HSP90 (but not HSP70) is additionally increased by the action of indopicin, canavanine or an alcoholic extract of the legume Indigofera spicata. Thus, blocking individual heat shock proteins in combination therapy based on arginine starvation can potentially increase its effectiveness. Product Description popup.authors Vovk Olena I. Vorobets Zinovii D. Danyleichenko Valerii V. Demash Dmytro V. Polishchuk Nikita V. Stasyk Oleh V. Stasyk Olena Н. Chernyshuk Svitlana V Shuvaieva Halyna Yu. popup.nrat_date 2025-01-25 Close