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

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

Fingerprint

Gonadotropin-Releasing Hormone
Growth
Estradiol
Ovarian epithelial cancer
In Vitro Techniques
Binding Sites
Ligands
LHRH Receptors
Hormone Antagonists
LH Receptors
Thymidine
Cultured Cells
Estrogens
Cell Count
Cell Proliferation
Cell Line
Temperature

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

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title = "Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone",
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.",
keywords = "[H]thymidine incorporation, cell proliferation, gynecologic cancer, luteinizing hormone- releasing hormone receptor",
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T1 - Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone

AU - Yano, Tetsu

AU - Pinski, Jacek

AU - Radulovic, Sinisa

AU - Schally, Andrew V

PY - 1994/3/1

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N2 - 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.

AB - 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.

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