Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone

Tetsu Yano, Jacek Pinski, Sinisa Radulovic, Andrew V. Schally

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

In this study, we investigated the effects of luteinizing hormone- releasing hormone (LH-RH) agonist [D-Trp6]LH-RH, LH-RH antagonist [Ac-D- Na](2)1, D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), and estradiol on the growth of human epithelial ovarian cancer cell line OV- 1063. Cells were cultured under estrogen-deprived conditions. Estradiol inhibited cell proliferation, as measured by cell number at 10-9-10-7 M and [3H]thymidine incorporation into DNA at 10-13-10-8 M. Both LH-RH analogs inhibited cell growth dose dependently in the range 10-8-10-5 M, but SB-75 induced a greater growth inhibition than [D-Trp6]LH-RH. In OV- 1063 cells, 125I-labeled [D-Trp6]LH-RH was bound to one class of specific, saturable binding sites with high affinity (K(d) = 1.4 ± 0.3 nM) and low capacity (4000 binding sites per cell). 125I-labeled [D-Trp6]LH- RH could be displaced by unlabeled [D-Trp6]LH-RH and SB-75, suggesting that both analogs are bound to the same receptor on OV-1063 cells. Ligand binding was dependent on time and temperature. Receptor internalization assay showed that the ligand-receptor complex was internalized at 37°C, which indicates the presence of biologically active LH-RH receptors on OV-1063 cells. These results suggest that estradiol and LH-RH analogs can suppress the growth of OV-1063 human epithelial ovarian cancer cells by a direct action and that the inhibitory effect of LH-RH analogs is mediated through the high-affinity LH- RH receptors.

Original languageEnglish (US)
Pages (from-to)1701-1705
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number5
DOIs
StatePublished - Mar 1 1994
Externally publishedYes

Keywords

  • [H]thymidine incorporation
  • cell proliferation
  • gynecologic cancer
  • luteinizing hormone- releasing hormone receptor

ASJC Scopus subject areas

  • Genetics
  • General

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