The cytosolic
5'-nucleotidase cN-II is a highly conserved
enzyme implicated in
nucleotide metabolism. Based on recent observations suggesting additional roles not directly associated to its enzymatic activity, we studied human
cancer cell models with basal or decreased cN-II expression. We developed
cancer cells with stable inhibition of cN-II expression by transfection of
shRNA-coding plasmids, and studied their biology. We show that human
breast cancer cells MDA-MB-231 with decreased cN-II expression better adapt to the disappearance of
glucose in growth medium under normoxic conditions than cells with a baseline expression level. This is associated with enhanced in vivo growth and a lower content of ROS in cells cultivated in absence of
glucose due to more efficient mechanisms of elimination of ROS. Conversely, cells with low cN-II expression are more sensitive to
glucose deprivation in hypoxic conditions. Overall, our results show that cN-II regulates the cellular response to
glucose deprivation through a mechanism related to ROS metabolism and defence.