We have previously demonstrated that arginine deiminase inhibits the prolif
eration of vascular endothelial cells, but the mechanisms leading to growth
inhibition leave remained unclear. We report here that low concentrations
of arginine deiminase purified from Mycoplasma arginini inhibit proliferati
on of various cultured cells by arresting the cell cycle in G(1) and/or S p
hase with higher arginine deiminase concentrations leading to subsequent ap
optosis, Our results demonstrate that arginine deiminase inhibits cell. pro
liferation not only by depletion of arginine, but also by mechanisms involv
ing the cell cycle and death signals. (C) 1999 Academic Press.