Induction of apoptosis in ovarian carcinoma cell line by gonadotropin-releasing hormone agonist.

Abstract

Gonadotropin releasing hormone (GnRH) agonist suppresses the growth of the cancer cells in vitro. To evaluate the effect of a GnRH agonist (GnRHA) in ovarian carcinomas, we investigated the interactions of GnRHA with the KOC-2s human ovarian cancer cells. The addition of GnRHA (10(-8)-10(-6)M) produced an increase 20-30% in the number of cells (p < 0.05). GnRHA (10(-5) M) produced a slight, statistically insignificant decrease of < 10% in the cell count. No DNA fragmentation was produced by GnRHA (10(-8)-10(-6)M). However, GnRHA (10(-5)M) produced internucleosomal cleavage of DNA into fragments with multiples of 180 to 200 bp. This DNA "ladder" pattern is characteristic of apoptosis. The amount of Fas antigen was reduced by each concentration of GnRHa. The addition of GnRHA (10(-6)M and 10(-5)M) significantly increased the secretion of TNF-alpha (p < 0.001). The time- and dose-dependent effects of GnRHA might be confined to the KOC-2s cells as demonstrated by growth inhibitions and characteristic internucleosomal DNA fragmentation. However, the effects of GnRHA on secretion of TNF-alpha and the expression of Fas antigen differed. The present results provide a basis for future studies on the mechanism of apoptotic effect of GnRHA.