Effect of polaprezinc ( N-(3-aminopropionyl)- l-histidinato zinc), a novel antiulcer agent containing zinc, on cellular proliferation: role of insulin-like growth factor I

Abstract

The effect of polaprezinc ( N-(3-aminopropionyl)- l-histidinato zinc), a novel antiulcer drug containing zinc, on cellular proliferation was studied using cultured cells. In human umbilical vein endothelial cells (HUVEC) or human foreskin fibroblast cells, bromodeoxyuridine (BrdU) uptake and the number of cells were increased by polaprezinc under low serum conditions, but polaprezinc had no effect on guinea pig gastric mucosal epithelial cells. In addition, l-carnosine (a component of polaprezinc) had no effect on cultured HUVEC, while zinc sulfate, a representative zinc compound, increased BrdU uptake by about 2-fold at 10 −9 M. However, the action of zinc sulfate was weaker than that of polaprezinc. The insulin-like growth factor I (IGF-I) mRNA level was increased in HUVEC by polaprezinc at 10 −9 M ∼ 3 × 10 −8 M concentrations, causing stimulation of BrdU uptake. When an anti-IGF-I antibody was added to cultures, the effects of polaprezinc on BrdU uptake was suppressed. These results suggest that although polaprezinc, a novel antiulcer agent, does not have proliferative effects on epithelial cells, it does promote the proliferation of non-parenchymal cells, and IGF-I is involved in this action.