Work

The aim of the proposed scientific works series was the development of the new combinational anticancer approach based on amino acid arginine starvation and its in vitro testing on the model of three-dimensional human tumor spheroids. The search for the new methods of cancer treatment is an urgent need of our time. Despite the obvious success in the understanding of the molecular basis of human tumors origination, the death rate between cancer patients still remains far too high. Therefore, the development of the new targeted combinational oncotherapeutic approaches and the search for the model systems for the appropriate testing of the antitumor properties of these approaches is a crucial task of modern medicine and cellular biology. As a result of the conducted studies a new experimental anticancer approach based on the combined application of the recombinant arginine-degrading enzyme arginase, the arginine natural analogue canavanine and X-rays irradiation was developed. The correlation between tumor cells p53-status and the level of sensitivity of those cells to arginine deprivation was observed. We are first to develop the detailed protocols of the experiments for the analysis of the effect of a single amino acid starvation on human tumor cells when cultured in the form of three-dimensional multicellular spheroids. It was shown for the first time that when applied under arginine starved conditions, the arginine natural analogue canavanine is selectively toxic for human cancer cells. We are first to reveal the radiosensitizing properties of the recombinant arginine-degrading enzyme arginase and its combination with canavanine. The results of the presented studies were confirmed on the model of 10 monolayer human epithelial cancer cell lines and 4 spheroid tumor cell types. The correlation was found between the results obtained in three-dimensional spheroid cell culture and the literary data on clinical trials on cancer patients. The scientific works series consists of 35 publications, including 4 papers (3 of them are published in the international journals with total impact factor of 9.6) and 31 abstracts in the collected materials of the home and international conferences that were published during 2008–2012.