Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis

Leukotriene D4 (LTD4) is a pro-inflammatory mediator formed from arachidonic acid through the action of 5-lipoxygenase (5-LOX). Its biological effects are mediated by at least two G-coupled plasmatic cysteinyl LT receptors (CysLT1-2R). It has been reported an upregulation of the 5-LOX pathway in tum...

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Autores: Cabral Salvadores, Marisol, Martín Venegas, Raquel, Moreno Aznárez, Juan José
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/163679
Acesso em linha:https://hdl.handle.net/2445/163679
Access Level:acceso abierto
Palavra-chave:Càncer colorectal
Cèl·lules canceroses
Àcid araquidònic
Colorectal cancer
Cancer cells
Arachidonic acid
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spelling Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesisCabral Salvadores, MarisolMartín Venegas, RaquelMoreno Aznárez, Juan JoséCàncer colorectalCèl·lules cancerosesÀcid araquidònicColorectal cancerCancer cellsArachidonic acidLeukotriene D4 (LTD4) is a pro-inflammatory mediator formed from arachidonic acid through the action of 5-lipoxygenase (5-LOX). Its biological effects are mediated by at least two G-coupled plasmatic cysteinyl LT receptors (CysLT1-2R). It has been reported an upregulation of the 5-LOX pathway in tumor tissue unlike in normal colon mucosa. Colon tumors generally have an increased expression of CysLT1R and colon cancer patients with high expression levels of CysLT1R have poor prognosis. We previously observed that the cyclooxygenase pathway is involved in the control of intestinal epithelial cancer cell growth through PGE2 production. The aim of this study was therefore to assess the effect of LTD4 binding with CysLT1R on Caco-2 cell growth. We note a number of key findings from this research. We observed that at a concentration similar to that found under inflammatory conditions, LTD4 was able to induce Caco-2 cell proliferation and DNA synthesis. Moreover, with the use of a specific receptor antagonist this study has demonstrated that the effect of LTD4 is a result of its interaction with CystLT1R. We also note the possible participation of the PLC-IP3-Ca2+/DAG-PKC signaling pathways in cytosolic PLA2 and [3H]AA release induced by LTD4-CystLT1R interaction. Finally, we found that the resulting activation of the AA cascade and the production of PGE2 eicosanoid could be related to the activation of cell signaling pathways such as ERK and CREB. These findings will help facilitate our understanding of how inflammatory mediators can affect the survival and dissemination of intestinal carcinoma cells.Wiley2020202020152020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion7 p.application/pdfhttps://hdl.handle.net/2445/163679Articles publicats en revistes (Bioquímica i Fisiologia)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.14814/phy2.12417Physiological Reports, 2015, vol. 3, num. 7, p. e12417https://doi.org/10.14814/phy2.12417cc-by (c) Cabral Salvadores, Marisol et al., 2015http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1636792026-05-29T05:05:01Z
dc.title.none.fl_str_mv Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
title Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
spellingShingle Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
Cabral Salvadores, Marisol
Càncer colorectal
Cèl·lules canceroses
Àcid araquidònic
Colorectal cancer
Cancer cells
Arachidonic acid
title_short Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
title_full Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
title_fullStr Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
title_full_unstemmed Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
title_sort Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis
dc.creator.none.fl_str_mv Cabral Salvadores, Marisol
Martín Venegas, Raquel
Moreno Aznárez, Juan José
author Cabral Salvadores, Marisol
author_facet Cabral Salvadores, Marisol
Martín Venegas, Raquel
Moreno Aznárez, Juan José
author_role author
author2 Martín Venegas, Raquel
Moreno Aznárez, Juan José
author2_role author
author
dc.subject.none.fl_str_mv Càncer colorectal
Cèl·lules canceroses
Àcid araquidònic
Colorectal cancer
Cancer cells
Arachidonic acid
topic Càncer colorectal
Cèl·lules canceroses
Àcid araquidònic
Colorectal cancer
Cancer cells
Arachidonic acid
description Leukotriene D4 (LTD4) is a pro-inflammatory mediator formed from arachidonic acid through the action of 5-lipoxygenase (5-LOX). Its biological effects are mediated by at least two G-coupled plasmatic cysteinyl LT receptors (CysLT1-2R). It has been reported an upregulation of the 5-LOX pathway in tumor tissue unlike in normal colon mucosa. Colon tumors generally have an increased expression of CysLT1R and colon cancer patients with high expression levels of CysLT1R have poor prognosis. We previously observed that the cyclooxygenase pathway is involved in the control of intestinal epithelial cancer cell growth through PGE2 production. The aim of this study was therefore to assess the effect of LTD4 binding with CysLT1R on Caco-2 cell growth. We note a number of key findings from this research. We observed that at a concentration similar to that found under inflammatory conditions, LTD4 was able to induce Caco-2 cell proliferation and DNA synthesis. Moreover, with the use of a specific receptor antagonist this study has demonstrated that the effect of LTD4 is a result of its interaction with CystLT1R. We also note the possible participation of the PLC-IP3-Ca2+/DAG-PKC signaling pathways in cytosolic PLA2 and [3H]AA release induced by LTD4-CystLT1R interaction. Finally, we found that the resulting activation of the AA cascade and the production of PGE2 eicosanoid could be related to the activation of cell signaling pathways such as ERK and CREB. These findings will help facilitate our understanding of how inflammatory mediators can affect the survival and dissemination of intestinal carcinoma cells.
publishDate 2015
dc.date.none.fl_str_mv 2015
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/163679
url https://hdl.handle.net/2445/163679
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.14814/phy2.12417
Physiological Reports, 2015, vol. 3, num. 7, p. e12417
https://doi.org/10.14814/phy2.12417
dc.rights.none.fl_str_mv cc-by (c) Cabral Salvadores, Marisol et al., 2015
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Cabral Salvadores, Marisol et al., 2015
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 7 p.
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Fisiologia)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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