Involvement of annexin V in the antiproliferative effect of GnRH agonist on cultured human uterine leiomyoma cells

The objective of this study was to elucidate the role of annexin V, an endo genous inhibitor of protein kinase C (PKC), with regard to the antiprolifer ative effect of gonadotrophin-releasing hormone (GnRH) agonist (buserelin) on cultured human uterine leiomyoma cells. Uterine leiomyoma tissue was col lected from the surgical specimens of patients and cells from 37 specimens (15 cases) were cultured. For up to 96 h after the addition of buserelin to the cultured cells, a time-dependent antiproliferative effect was noted in the group to which 10(-5) mol/I buserelin was added. Both the intracellula r concentration of annexin V and the expression of annexin V mRNA increased time-dependently with the addition of buserelin, The intracellular concent ration of annexin V increased with the addition of PKC activator ( 12-O-tet radecanoylphorbor- 13-acetate; TPA) much as it did with the addition of bus erelin, and the rise in the concentration caused by the addition of buserel in was completely attenuated by pretreatment with PKC inhibitor (calphostin C). Our findings suggest that buserelin inhibits cell proliferation in cul tured human uterine leiomyoma cells accompanied with an increase in the int racellular concentration of annexin V, mediated, at least in part, by the a ctivation of PKC.