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SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo
SR31747A is a recently described sigma receptor ligand that binds SR31747A-binding protein 1 (SR-BP) and emopamil-binding protein (EBP) (also called the sigma1 receptor and the human sterol isomerase (HSI), respectively), and has immunoregulatory and antiproliferative activities. To further investig...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747535/ https://www.ncbi.nlm.nih.gov/pubmed/12569389 http://dx.doi.org/10.1038/sj.bjc.6600709 |
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author | Berthois, Y Bourrié, B Galiègue, S Vidal, H Carayon, P Martin, P M Casellas, P |
author_facet | Berthois, Y Bourrié, B Galiègue, S Vidal, H Carayon, P Martin, P M Casellas, P |
author_sort | Berthois, Y |
collection | PubMed |
description | SR31747A is a recently described sigma receptor ligand that binds SR31747A-binding protein 1 (SR-BP) and emopamil-binding protein (EBP) (also called the sigma1 receptor and the human sterol isomerase (HSI), respectively), and has immunoregulatory and antiproliferative activities. To further investigate its antitumour activity and focusing on cancers, which are sensitive to the molecule, we measured the proliferation of different human epithelial breast or prostate cancer cell lines following in vitro and in vivo SR31747A treatment. Firstly, in vitro, we found that nanomolar concentrations of SR31747A dramatically inhibited cell proliferation in both hormono-responsive and -unresponsive cancer cell lines. Secondly, tumour development was significantly decreased in mice treated with SR31747A. In an attempt to decipher the SR31747A mode of action, we found that the two binding sites may not fully account for this activity. Indeed, while competitive experiments indicated that EBP prevails in mediating SR31747A antiproliferative activity, an analysis of the expression of both receptors indicated that the cellular sensitivity to SR31747A is not correlated with either EBP or SR-BP expression. These data suggest that additional binding sites may exist. Preliminary binding studies demonstrated that SR31747A also binds to sigma2, a protein that has not yet been cloned, but which is considered as a potential marker of the proliferative status of tumour cells. Altogether, our data demonstrate the antitumoural activity of SR31747A both in vitro and in vivo in two different cancer models, broaden the spectrum of its binding proteins and enhance the potential for further therapeutic development of the molecule. |
format | Text |
id | pubmed-2747535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-27475352009-09-21 SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo Berthois, Y Bourrié, B Galiègue, S Vidal, H Carayon, P Martin, P M Casellas, P Br J Cancer Experimental Therapeutics SR31747A is a recently described sigma receptor ligand that binds SR31747A-binding protein 1 (SR-BP) and emopamil-binding protein (EBP) (also called the sigma1 receptor and the human sterol isomerase (HSI), respectively), and has immunoregulatory and antiproliferative activities. To further investigate its antitumour activity and focusing on cancers, which are sensitive to the molecule, we measured the proliferation of different human epithelial breast or prostate cancer cell lines following in vitro and in vivo SR31747A treatment. Firstly, in vitro, we found that nanomolar concentrations of SR31747A dramatically inhibited cell proliferation in both hormono-responsive and -unresponsive cancer cell lines. Secondly, tumour development was significantly decreased in mice treated with SR31747A. In an attempt to decipher the SR31747A mode of action, we found that the two binding sites may not fully account for this activity. Indeed, while competitive experiments indicated that EBP prevails in mediating SR31747A antiproliferative activity, an analysis of the expression of both receptors indicated that the cellular sensitivity to SR31747A is not correlated with either EBP or SR-BP expression. These data suggest that additional binding sites may exist. Preliminary binding studies demonstrated that SR31747A also binds to sigma2, a protein that has not yet been cloned, but which is considered as a potential marker of the proliferative status of tumour cells. Altogether, our data demonstrate the antitumoural activity of SR31747A both in vitro and in vivo in two different cancer models, broaden the spectrum of its binding proteins and enhance the potential for further therapeutic development of the molecule. Nature Publishing Group 2003-02-10 2003-02-10 /pmc/articles/PMC2747535/ /pubmed/12569389 http://dx.doi.org/10.1038/sj.bjc.6600709 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Experimental Therapeutics Berthois, Y Bourrié, B Galiègue, S Vidal, H Carayon, P Martin, P M Casellas, P SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo |
title | SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo |
title_full | SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo |
title_fullStr | SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo |
title_full_unstemmed | SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo |
title_short | SR31747A is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo |
title_sort | sr31747a is a sigma receptor ligand exhibiting antitumoural activity both in vitro and in vivo |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747535/ https://www.ncbi.nlm.nih.gov/pubmed/12569389 http://dx.doi.org/10.1038/sj.bjc.6600709 |
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