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The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer
Auteur(s) : Cousin, Fabien, Jouan, Sandrine, Théret, Nathalie Brenner, Catherine Jouan, Elodie, Le Moigne-Muller, Gwénaël Dimanche-Boitrel, Marie-Thérèse Jan¨, Gwénaël,
Auteurs secondaires : Aliments Bioprocédés Toxicologie Environnements (ABTE) ; Université de Caen Normandie (UNICAEN) ; Normandie Université (NU) - Normandie Université (NU) - Université de Rouen Normandie (URN) ; Normandie Université (NU) - Institut de Biologie Fondamentale et Appliquée [Caen] (IBFA) Centre National Interprofessionnel de l'Economie Laitière [Paris] (CNIEL) Science et Technologie du Lait et de l'Oeuf (STLO) ; Institut National de la Recherche Agronomique (INRA) - AGROCAMPUS OUEST 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 ) Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) Faculté de Pharmacie [Châtenay-Malabry] ; Université Paris-Sud 11 - Faculté de médecine (UP11 UFR Médecine) - Université Paris-Saclay Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique [Châtenay-Malabry] (LabEx LERMIT) ; Université Paris-Sud - Paris 11 (UP11) - Institut National de la Santé et de la Recherche Médicale

Éditeur(s) : HAL CCSD Impact journals
Résumé : International audience
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.
ISSN: 1949-2553

hal-01404971
https://hal.inria.fr/hal-01404971
https://hal.inria.fr/hal-01404971/document
https://hal.inria.fr/hal-01404971/file/2016%20Oncotarget_The%20probiotic%20Propionibacterium%20freudenreichii%20as%20a%20new%20adjuvant%20for%20TRAIL-based%20therapy%20in%20colorectal%20cancer..pdf
DOI : 10.18632/oncotarget.6881

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