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 language | English |
|---|---|
| Pages (from-to) | 1701-1705 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 91 |
| Issue number | 5 |
| State | Published - Mar 1 1994 |
| Externally published | Yes |
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Keywords
- [H]thymidine incorporation
- cell proliferation
- gynecologic cancer
- luteinizing hormone- releasing hormone receptor
ASJC Scopus subject areas
- Genetics
- General
Cite this
Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone. / Yano, Tetsu; Pinski, Jacek; Radulovic, Sinisa; Schally, Andrew V.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 5, 01.03.1994, p. 1701-1705.Research output: Contribution to journal › Article
}
TY - JOUR
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
Y1 - 1994/3/1
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.
KW - [H]thymidine incorporation
KW - cell proliferation
KW - gynecologic cancer
KW - luteinizing hormone- releasing hormone receptor
UR - http://www.scopus.com/inward/record.url?scp=0028203309&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028203309&partnerID=8YFLogxK
M3 - Article
VL - 91
SP - 1701
EP - 1705
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 5
ER -