The probiotic Propionibacterium freudenreichii as a new adjuvant for TRAIL-based therapy in colorectal cancer

Oncotarget
Fabien J CousinGwénaël Jan

Abstract

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 ...Continue Reading

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Citations

May 16, 2017·Microorganisms·Houem RabahGwénaël Jan
May 29, 2016·Applied and Environmental Microbiology·Song HuangGwénaël Jan
Jul 13, 2019·Nature Reviews. Gastroenterology & Hepatology·Mary Ellen SandersRobert A Rastall
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Aug 11, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Tianqing SangHongguang Zhou
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Jan 14, 2021·Radiation Oncology·Jing LiuJinbo Yue
Apr 23, 2021·Applied Microbiology and Biotechnology·Romain Jeantet, Gwénaël Jan
Jul 3, 2021·Cancers·Ashutosh TripathyManoj Kumar Jena

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Methods Mentioned

BETA
xenografts
flow cytometry
acetylation
fluorescence microscopy
Flow
acetylate
histone acetylation
FCS
Feature Extraction

Software Mentioned

Resolver
Agilent 2100 Bioanalyzer
Rosetta
FatiGo
Rosetta Resolver R
Babelomics
Agilent Feature Extraction Software ( FES )

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