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Information × Registration Number 0219U000870, 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 07-03-2019 Organization Institute of cell biology, National Academy of Sciences of Ukraine popup.description2 The combined impact of arginine deficiency and modulators of endoplasmic reticulum (ER) homeostasis on the viability of head and neck tumor cells was investigated. It was shown that these cells substantially differ by their sensitivity to arginine deprivation. It was revealed that arginine deficit induces apoptotic death of SAS cells but the addition of the ER stress inhibitor salubrinal reduces both ER stress and cell death. However, the combined action of arginine analogue canavanine and arginine deficit induces ER stress activation and ER-stress-mediated apoptosis in head and neck tumor cells. Thus, the combination of arginine deficit, canavanine and additional selective modulators of ER stress potentially can be provided with a new strategy for treatment of head and neck tumors. It was established that canavanine causes the increasing of ER stress level as well as autophagy induction in ovarian carcinoma SKOV3 cells under arginine deprivation. The proliferation inhibition and tumor cell death are the consequences of these processes. The influence of combined therapy based on arginine deprivation on proapoptotic and antiapoptotic cell pathways regulation under ER stress induction was performed. It was established that addition of arginine analogues, canavanine and thioarginine, to human colorectal carcinoma HCT116 cells cultivated in arginine-free medium, enhance ER stress level. This activation leads to disturbance in gene expression of transcription factors cMyc andі HIF1-alpha as well as MAPK, AKT-mTOR and AMPK signaling cascade functioning. In turn, these processes cause cell viability decreasing and induction of caspase-dependent apoptosis. Product Description popup.authors Бобак Я.П. Вовк О.І. Данилейченко В.В. Маєвська О.М. Сибірна Н.О. Чень О.І. Чернишук С.В. Шуваєва Г.Ю. popup.nrat_date 2020-04-02 Close