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Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity
In addition to its primary role as growth factor, human growth hormone (hGH) can also participate in cell survival, as already documented by its protective effect on human monocytes or human promyelocytic leukaemia U937 cells exposed to a Fas-mediated cell death signal. However, despite similarities...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2003
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376966/ https://www.ncbi.nlm.nih.gov/pubmed/12966434 http://dx.doi.org/10.1038/sj.bjc.6601223 |
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author | Cherbonnier, C Déas, O Carvalho, G Vassal, G Dürrbach, A Haeffner, A Charpentier, B Bénard, J Hirsch, F |
author_facet | Cherbonnier, C Déas, O Carvalho, G Vassal, G Dürrbach, A Haeffner, A Charpentier, B Bénard, J Hirsch, F |
author_sort | Cherbonnier, C |
collection | PubMed |
description | In addition to its primary role as growth factor, human growth hormone (hGH) can also participate in cell survival, as already documented by its protective effect on human monocytes or human promyelocytic leukaemia U937 cells exposed to a Fas-mediated cell death signal. However, despite similarities in the molecular events following Fas and TNF-α receptor engagement, we report that U937 cells, genetically engineered to constitutively produce hGH, were made more sensitive to TNF-α-induced apoptosis than parental cells. This was due to overproduction of the antioxidant glutathione, which decreased the nuclear factor (NF)-κB activity known to control the expression of survival genes. These findings were confirmed in vivo, in nude mice bearing U937 tumours coinjected with recombinant hGH and the NF-κB -inducing anticancer drug daunorubicin, to avoid the in vivo toxicity of TNF-α. This study therefore highlights one of the various properties of hGH that may have potential clinical implications. |
format | Text |
id | pubmed-2376966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2003 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23769662009-09-10 Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity Cherbonnier, C Déas, O Carvalho, G Vassal, G Dürrbach, A Haeffner, A Charpentier, B Bénard, J Hirsch, F Br J Cancer Experimental Therapeutics In addition to its primary role as growth factor, human growth hormone (hGH) can also participate in cell survival, as already documented by its protective effect on human monocytes or human promyelocytic leukaemia U937 cells exposed to a Fas-mediated cell death signal. However, despite similarities in the molecular events following Fas and TNF-α receptor engagement, we report that U937 cells, genetically engineered to constitutively produce hGH, were made more sensitive to TNF-α-induced apoptosis than parental cells. This was due to overproduction of the antioxidant glutathione, which decreased the nuclear factor (NF)-κB activity known to control the expression of survival genes. These findings were confirmed in vivo, in nude mice bearing U937 tumours coinjected with recombinant hGH and the NF-κB -inducing anticancer drug daunorubicin, to avoid the in vivo toxicity of TNF-α. This study therefore highlights one of the various properties of hGH that may have potential clinical implications. Nature Publishing Group 2003-09-15 2003-09-09 /pmc/articles/PMC2376966/ /pubmed/12966434 http://dx.doi.org/10.1038/sj.bjc.6601223 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 Cherbonnier, C Déas, O Carvalho, G Vassal, G Dürrbach, A Haeffner, A Charpentier, B Bénard, J Hirsch, F Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity |
title | Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity |
title_full | Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity |
title_fullStr | Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity |
title_full_unstemmed | Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity |
title_short | Potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased NF-κB activity |
title_sort | potentiation of tumour apoptosis by human growth hormone via glutathione production and decreased nf-κb activity |
topic | Experimental Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2376966/ https://www.ncbi.nlm.nih.gov/pubmed/12966434 http://dx.doi.org/10.1038/sj.bjc.6601223 |
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