INHIBITION OF HUMAN HEPATOCARCINOMA CELL-PROLIFERATION BY MAMMALIAN AND FISH GONADOTROPIN-RELEASING HORMONES

This study provides the first demonstration that human hepatocarcinoma -derived cell line HepG2 contains GnRR receptors and responds to vario us molecular forms of GnRH in terms of inhibition of proliferation in a time- and dose-related manner. In addition, GnRH peptides also signi ficantly inhibited the uptake of [H-3]thymidine by these cells. The ef fect of GnRH was specific because GnRH antagonists reversed the GnRH-m ediated inhibition, and non-GnRH peptides had no effect on HepG2 cell proliferation. An important finding is that certain fish GnRH molecule s such as lamprey GnRH, which has little gonadotropin (LH) release act ivity in mammals, suppress hepatocarcinoma cell proliferation with sim ilar potency to a superactive mammalian GnRH analog, [D-Lys(6)]GnRH. T hese findings may have profound implications in the development of an effective chemotherapy for treatment of human liver cancer. An added a dvantage is that fish GnRH forms will likely exert little side effect in terms of human pituitary gonadotropin release, gonadal steroidogene sis, and reproductive functions in general.