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<title lang=en>The probiotic [i]Propionibacteriumfreudenreichii[/i] as a new adjuvant for TRAIL-based therapy in colorectal cancer</title>
<creator>Cousin, Fabien</creator>
<creator>Jouan-Lanhouet, S.</creator>
<creator>Théret, Nathalie</creator>
<creator>Brenner, C.</creator>
<creator>Jouan, E.</creator>
<creator>Le Moigne-Muller, Gwenaëlle</creator>
<creator>Dimanche-Boitrel, Marie-Thérèse</creator>
<contributor>Science et Technologie du Lait et de l'Oeuf (STLO) ; Institut National de la Recherche Agronomique (INRA) - AGROCAMPUS OUEST</contributor>
<contributor>Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )</contributor>
<contributor>Dynamics, Logics and Inference for biological Systems and Sequences (Dyliss) ; GESTION DES DONNÉES ET DE LA CONNAISSANCE (IRISA-D7) ; Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA) ; CentraleSupélec - Université de Rennes 1 (UR1) - Télécom Bretagne - Institut National des Sciences Appliquées (INSA) - Institut National de Recherche en Informatique et en Automatique (Inria) - École normale supérieure - Rennes (ENS Rennes) - Centre National de la Recherche Scientifique (CNRS) - Université de Bretagne Sud (UBS) - CentraleSupélec - Université de Rennes 1 (UR1) - Télécom Bretagne - Institut National des Sciences Appliquées (INSA) - Institut National de Recherche en Informatique et en Automatique (Inria) - École normale supérieure - Rennes (ENS Rennes) - Centre National de la Recherche Scientifique (CNRS) - Université de Bretagne Sud (UBS) - Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA) ; CentraleSupélec - Université de Rennes 1 (UR1) - Télécom Bretagne - Institut National des Sciences Appliquées (INSA) - Institut National de Recherche en Informatique et en Automatique (Inria) - École normale supérieure - Rennes (ENS Rennes) - Centre National de la Recherche Scientifique (CNRS) - Université de Bretagne Sud (UBS) - CentraleSupélec - Université de Rennes 1 (UR1) - Télécom Bretagne - Institut National des Sciences Appliquées (INSA) - Institut National de Recherche en Informatique et en Automatique (Inria) - École normale supérieure - Rennes (ENS Rennes) - Centre National de la Recherche Scientifique (CNRS) - Université de Bretagne Sud (UBS) - Inria Rennes – Bretagne Atlantique ; Institut National de Recherche en Informatique et en Automatique (Inria)</contributor>
<contributor>Institut de Recherche sur la Santé, l'Environnement et le Travail ; Institut National de la Santé et de la Recherche Médicale (INSERM)</contributor>
<contributor>Faculté de Pharmacie ; Université Paris-Sud - Paris 11 (UP11)</contributor>
<contributor>SIGNALISATION ET PHYSIOPATHOLOGIE CARDIOVASCULAIRE (UMRS1180, LabEx LERMIT) ; Institut National de la Santé et de la Recherche Médicale</contributor>
<source>4 . International Symposium on Propionibacteria and Bibfidobacteria </source>
<coverage>Cork, Ireland</coverage>
<identifier>hal-01372131</identifier>
<identifier>https://hal.archives-ouvertes.fr/hal-01372131</identifier>
<source>https://hal.archives-ouvertes.fr/hal-01372131</source>
<source>4 International Symposium on Propionibacteria and Bibfidobacteria , Sep 2016, Cork, Ireland. 2016</source>
<identifier>PRODINRA : 371605</identifier>
<language>en</language>
<subject lang=en>probiotique</subject>
<subject lang=en>produit laitier</subject>
<subject lang=en>propionibacterium freudenreichi</subject>
<subject lang=en>cancer colo-rectale</subject>
<subject lang=en>santé humaine</subject>
<subject>[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition</subject>
<subject>[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology</subject>
<subject>[SDV.IDA] Life Sciences [q-bio]/Food engineering</subject>
<type>info:eu-repo/semantics/conferenceObject</type>
<type>Poster communications</type>
<description lang=en>TNF-Related Apoptosis-Inducing Ligand (TRAIL) is a well-known apoptosis inducer, which activates the extrinsic death pathway. TRAIL is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by cell resistance to cell death which occurs in approximately 50% of cancer cells. Short Chain Fatty Acids (SCFA) are also known to specifically induce apoptosis of cancer cells. In accordance, we have shown that food grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via the production and release of SCFA (propionate and acetate) acting on mitochondria. Here, we investigated possible synergistic effect between Propionibacterium freudenreichii and TRAIL. Indeed, we hypothesized that acting on both extrinsic and intrinsic death pathways may exert a synergistic pro-apoptotic effect. Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial metabolites (propionate and acetate), in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIP, XIAP) in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on both death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and caspases (caspase-8, -9 and -3) activation, was lethal on cancer cells but not on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented by P. freudenreichii induced HT29 cells apoptosis and enhanced TRAIL cytotoxic activity, as did P. freudenreichii DMEM culture supernatants or its SCFA metabolites. These results open new perspectives for food grade P. freudenreichii-containing products in order to potentiate TRAIL-based cancer therapy in colorectal cancer. </description>
<date>2016-09-20</date>
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