EFFECT OF COMBINED ARGINASE AND NITRIC OXIDE DONOR TREATMENT ON NORMAL AND LEUKEMIC CELLS IN VITRO
DOI: http://dx.doi.org/10.30970/sbi.1001.470
Abstract
Arginine deprivation has been recently suggested as a therapeutic approach against difficult to cure blood cancers. Herein, we investigated for the first time the combined effect of exogenous nitric oxide (NO) donor and recombinant human arginase (rhARG) as arginine-depleting agent on viability of several human leukemic cell lines and normal peripheral blood lymphocytes (PBL). We found that exogenous NO donor, sodium nitroprusside (SNP), at physiologically compatible dose did not counteract but augmented rhARG-mediated pro-apoptotic effect of arginine depletion in leukemic cells but not in resting lymphocytes. Thus, we hypothesize that NO deficiency resulting from arginine deprivation is not the primary cause of high leukemic cells sensitivity to the action of rhARG. The results of this study further support the notion that not arginine catabolism but other cell response mechanisms must be involved in determining cell fate upon arginine restriction. SNP or alternative NO donors can be proposed as components of metabolic anti-leukemia therapy based on arginine deprivation.
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