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| Status |
Public on Feb 01, 2016 |
| Title |
The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
TRAIL (TNF-Related Apoptosis Inducing Ligand) is a well-known apoptosis inducer, which activates the extrinsic death pathway. It is pro-apoptotic on colon cancer cells, while not cytotoxic towards normal healthy cells. However, its clinical use is limited by resistance which occurs in approximately 50% of cancer cells. SCFA (Short Chain Fatty Acids) 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/acetate) acting on mitochondria. Here, we investigated possible synergistic effect between Propionibacterium freudenreichii and TRAIL. 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, boosted pro-apoptotic gene expression in HT29 human colon cancer cells. The revealed synergistic pro-apoptotic effect, depending on death receptors (TRAIL-R1/DR4, TRAIL-R2/DR5) and on caspase-8, caspase-9 and caspase-3 activation, was more lethal on cancer cells than on normal human intestinal epithelial cells (HIEC), and was inhibited by Bcl-2 expression. Finally, milk fermented only by P. freudenreichii induced apoptosis of HT29 cells and enhanced cytotoxic activity of TRAIL, as did P. freudenreichii culture supernatants or its metabolites SCFA. These results open new perspectives for the use of food grade P. freudenreichii-containing products in order to potentiate TRAIL-based cancer therapy in colorectal cancer.
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| Overall design |
Cells were either untreated (reference sample) or treated with C3/C2 (propionate and acetate), SN (propionibacterial supernatant), TRAIL, TRAIL+C3/C2 and TRAIL+SN. Together, 6 different conditions in quadriplicate (24 experiments )
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| Contributor(s) |
Cousin FJ, Jouan-Lanhouet S, Théret N, Brenner C, Jouan E, LeMoigne-Muller G, Dimanche-Boitrel M, Jean G |
| Citation(s) |
26771233 |
| Submission date |
Mar 18, 2015 |
| Last update date |
Apr 23, 2018 |
| Contact name |
Nathalie THERET |
| Organization name |
University of Rennes 1
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| Department |
INSERM U1085
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| Street address |
2 avenue Pr Leon Bernard
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| City |
RENNES |
| ZIP/Postal code |
35043 |
| Country |
France |
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| Platforms (1) |
| GPL16699 |
Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Feature Number version) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA278756 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE67033_K1555_A4528_intensity_norm.txt.gz |
8.9 Mb |
(ftp)(http) |
TXT |
| GSE67033_RAW.tar |
295.9 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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