SR48692 is a neurotensin receptor antagonist which inhibits the growth of small cell lung cancer cells

Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. 3H-SR48692 bound with high affinity (IC 50 = 20 nM) to NCI-H209 cells. Also, NT and SR...

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Bibliographic Details
Published in:Peptides (New York, N.Y. : 1980) N.Y. : 1980), 2001, Vol.22 (1), p.109-115
Main Authors: Moody, Terry W, Chiles, Jessica, Casibang, Marchessini, Moody, Elizabeth, Chan, Daniel, Davis, Thomas P
Format: Article
Language:English
Subjects:
Animals
C-fos mRNA
Carcinoma, Small Cell - metabolism
Carcinoma, Small Cell - pathology
Cell Division - drug effects
Cytosolic Ca 2
Humans
Lung cancer
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Mice
Mice, Nude
Neoplasm Transplantation
Proliferation
Pyrazoles - pharmacology
Quinolines - pharmacology
Receptor binding
Receptors, Neurotensin - antagonists & inhibitors
Receptors, Neurotensin - metabolism
Signal Transduction - drug effects
SR48692
Tumor Cells, Cultured
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Summary:Neurotensin (NT) is an autocrine growth factor for some small cell lung cancer (SCLC) cells. In this communication, the effects of a non-peptide NT receptor antagonist, SR48692, were investigated using SCLC cells. 3H-SR48692 bound with high affinity (IC 50 = 20 nM) to NCI-H209 cells. Also, NT and SR48692 inhibited specific 125I-NT binding with high affinity (IC 50 values of 2 and 200 nM). In contrast, the NT 2 receptor agonist, levocabastine, had little effect on specific 125I-NT binding, second messenger production and proliferation using NCI-H209 cells. SR48692 (5 μM) antagonized the ability of NT (10 nM) to cause elevated cytosolic Ca 2+ in Fura-2 AM loaded NCI-H209 cells. SR48692 antagonized the ability of NT to cause elevation of c-fos mRNA in these cells. Using a MTT proliferation assay, SR48692 inhibited NCI-H209 and H345 proliferation in a concentration-dependent manner. Using a clonogenic assay, 1 μM SR48692, reduced NCI-H209 colony number. Also, SR48692 (0.4 mg/kg per day) inhibited NCI-H209 xenograft proliferation in nude mice. These results suggest that SR48692 is a NT 1 receptor antagonist which inhibits SCLC growth.
ISSN:0196-9781
1873-5169
DOI:10.1016/S0196-9781(00)00362-4