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Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum

Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB) pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after...

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Autores principales: Monteillier, Aymeric, Allard, Pierre-Marie, Gindro, Katia, Wolfender, Jean-Luc, Cuendet, Muriel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017800/
https://www.ncbi.nlm.nih.gov/pubmed/29534536
http://dx.doi.org/10.3390/molecules23030636
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author Monteillier, Aymeric
Allard, Pierre-Marie
Gindro, Katia
Wolfender, Jean-Luc
Cuendet, Muriel
author_facet Monteillier, Aymeric
Allard, Pierre-Marie
Gindro, Katia
Wolfender, Jean-Luc
Cuendet, Muriel
author_sort Monteillier, Aymeric
collection PubMed
description Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB) pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after for both cancer chemoprevention and therapy, and fungi represent an interesting unexplored reservoir for such molecules. The aim of the present work was to find naturally occurring lung cancer chemopreventive compounds by investigating the metabolites of Penicillium vulpinum, a fungus that grows naturally on dung. Penicillium vulpinum was cultivated in Potato Dextrose Broth and extracted with ethyl acetate. Bioassay-guided fractionation of this extract was performed by measuring NF-κB activity using a HEK293 cell line transfected with an NF-κB-driven luciferase reporter gene. The mycotoxin patulin was identified as a nanomolar inhibitor of TNF-α-induced NF-κB activity. Immunocytochemistry and Western blot analyses revealed that its mechanism of action involved an inhibition of p65 nuclear translocation and was independent from the NF-κB inhibitor α (IκBα) degradation process. Enhancing its interest in lung cancer chemoprevention, patulin also exhibited antiproliferative, proapoptotic, and antimigration effects on human lung adenocarcinoma cells through inhibition of the Wnt pathway.
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spelling pubmed-60178002018-11-13 Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum Monteillier, Aymeric Allard, Pierre-Marie Gindro, Katia Wolfender, Jean-Luc Cuendet, Muriel Molecules Article Lung cancer is the most lethal form of cancer in the world. Its development often involves an overactivation of the nuclear factor kappa B (NF-κB) pathway, leading to increased cell proliferation, survival, mobility, and a decrease in apoptosis. Therefore, NF-κB inhibitors are actively sought after for both cancer chemoprevention and therapy, and fungi represent an interesting unexplored reservoir for such molecules. The aim of the present work was to find naturally occurring lung cancer chemopreventive compounds by investigating the metabolites of Penicillium vulpinum, a fungus that grows naturally on dung. Penicillium vulpinum was cultivated in Potato Dextrose Broth and extracted with ethyl acetate. Bioassay-guided fractionation of this extract was performed by measuring NF-κB activity using a HEK293 cell line transfected with an NF-κB-driven luciferase reporter gene. The mycotoxin patulin was identified as a nanomolar inhibitor of TNF-α-induced NF-κB activity. Immunocytochemistry and Western blot analyses revealed that its mechanism of action involved an inhibition of p65 nuclear translocation and was independent from the NF-κB inhibitor α (IκBα) degradation process. Enhancing its interest in lung cancer chemoprevention, patulin also exhibited antiproliferative, proapoptotic, and antimigration effects on human lung adenocarcinoma cells through inhibition of the Wnt pathway. MDPI 2018-03-12 /pmc/articles/PMC6017800/ /pubmed/29534536 http://dx.doi.org/10.3390/molecules23030636 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Monteillier, Aymeric
Allard, Pierre-Marie
Gindro, Katia
Wolfender, Jean-Luc
Cuendet, Muriel
Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum
title Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum
title_full Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum
title_fullStr Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum
title_full_unstemmed Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum
title_short Lung Cancer Chemopreventive Activity of Patulin Isolated from Penicillium vulpinum
title_sort lung cancer chemopreventive activity of patulin isolated from penicillium vulpinum
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6017800/
https://www.ncbi.nlm.nih.gov/pubmed/29534536
http://dx.doi.org/10.3390/molecules23030636
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