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

The effect of polaprezinc (N-(3-aminopropionyl)-L-histidinato zinc), a nove l antiulcer drug containing zinc, on cellular proliferation was studied usi ng cultured cells. In human umbilical vein endothelial cells (HUVEC) or hum an foreskin fibroblast cells, bromodeoxyuridine (BrdU) uptake and the numbe r of cells were increased by polaprezine under low serum conditions, but po laprezinc had no effect on guinea pig gastric mucosal epithelial cells. In addition, L camosine (a component of poraprezinc) 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 polaprezine at: 10(-9) M similar to 3 x 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 u ptake was suppressed. These results suggest: that although polaprezinc, a n ovel antiulcer agent, does not have proliferative effects on epithelial cel ls, it does promote the proliferation of non-parenchymal cells, and IGF-I i s involved in this action. (C) 1999 Elsevier Science Inc.