Co-application of canavanine and irradiation uncouples anticancer potential of arginine deprivation from citrulline availability.

ABSTRACT: The moderate anticancer effect of arginine deprivation in clinical trials has been linked to an induced argininosuccinate synthetase (ASS1) expression in initially ASS1-negative tumors, and ASS1-positive cancers are anticipated as non-responders. Our previous studies indicated that arginine deprivation and low doses of the natural arginine analog canavanine can enhance radioresponse. However, the efficacy of the proposed combination in the presence of extracellular citrulline, the substrate for arginine synthesis by ASS1, remains to be elucidated, in particular for malignant cells with positive and/or inducible ASS1 as in colorectal cancer (CRC). Here, the physiological citrulline concentration of 0.05 mM was insufficient to overcome cell cycle arrest and radiosensitization triggered by ar

SUBMITTER: Kurlishchuk Y 

PROVIDER: S-EPMC5341980 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature