Kurlishchul Y. The impact of arginine deprivation combined with canavanine treatment and ionizing radiation on human colorectal cancer cells in vitro

Aim of the work: to determine the impact of arginine deprivation on the viability of human colorectal cancer cells in monolayer and spheroid culture in vitro and to investigate the anticancer potential of the proposed by us combination of arginine deprivation with its analog of plant origin, canavanine and radiation. Object of the research: the response of human colorectal cancer cells to arginine deprivation and its combination with canavanine and X-rays. Methods: Cell-biological, molecular biological and biochemical. It was shown that the regulation of translation under the lack of arginine determines the difference in sensitivity to arginine deprivation in the studies cancer cell lines as well as in the monolayer and spheroid cell culture of each cell line. It was revealed that not only the induction of ASS1 expression, but also the concentration of extracellular citrulline determines the growth and survival of the cancer cells in arginine-free medium. The low dose of canavanine intensifies cellular endoplasmic reticulum stress upon arginine deprivation and lead to the increased toxicity of this combination. It was shown for the first time that canavanine application inhibits induction of ASS1 expression and the ability of cancer cells to use citrulline for arginine synthesis. Combination of arginine deprivation with a low-dose canavanine treatment increases radiosensitivity of human colorectal cancer cells in spheroid culture regardless of the extracellular citrulline concentration.