Éditeur(s) : HAL CCSD
Résumé : Scope: TNF-Related Apoptosis-Inducing Ligand (TRAIL) induces apoptosis via the extrinsic death pathway in human colon cancer cells. Short Chain Fatty Acids (SCFA) by contrast induce apoptosis of cancer cells via the intrinsic death pathway. We have previously shown that food-grade dairy propionibacteria induce intrinsic apoptosis of colon cancer cells, via SCFA metabolites (propionate and acetate) acting on mitochondria. We investigate here the possible synergistic pro-apoptotic effect between Propionibacterium freudenreichii and TRAIL. Methods and results: Whole transcriptomic analysis demonstrated that propionibacterial supernatant or propionibacterial SCFA, in combination with TRAIL, increased pro-apoptotic gene expression (TRAIL-R2/DR5) and decreased anti-apoptotic gene expression (FLIPL, 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 culture supernatants or its SCFA metabolites.Conclusion: The revealed synergy opens new applications for food-grade P. freudenreichii-containing products as new adjuvants to potentiate TRAIL-based cancer therapy in colorectal cancer.
International Scientific Conference on Probiotics and Prebiotics - IPC2016
Budapest, Hungary

hal-01286497
https://hal.archives-ouvertes.fr/hal-01286497
PRODINRA : 349367

Éditeur(s) : HAL CCSD
Résumé : 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.
4 . International Symposium on Propionibacteria and Bibfidobacteria
Cork, Ireland

hal-01372131
https://hal.archives-ouvertes.fr/hal-01372131
PRODINRA : 371605