Gut microbiota-derived propionate reduces cancer cell proliferation in the liver
| العنوان: | Gut microbiota-derived propionate reduces cancer cell proliferation in the liver |
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| المؤلفون: | Laure B. Bindels, Olivier Feron, P Buc Calderon, J C Martin, Paolo E. Porporato, Julien Verrax, Pierre Sonveaux, Giulio G. Muccioli, Evelyne M. Dewulf, Nathalie M. Delzenne, Audrey M. Neyrinck, Patrice D. Cani, Karen P. Scott |
| المساهمون: | UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique, UCL - SSS/LDRI - Louvain Drug Research Institute, UCL - SSS/IREC - Institut de recherche expérimentale et clinique |
| المصدر: | British Journal of Cancer The British journal of cancer, Vol. 107, no. 8, p. 1337-1344 (2012) |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Cancer Research, Cell, Gut flora, Receptors, G-Protein-Coupled, Mice, inulin-type fructans, Free fatty acid receptor 2, medicine, Animals, propionate, Receptor, Molecular Diagnostics, Cell Proliferation, chemistry.chemical_classification, Mice, Inbred BALB C, Leukemia, gut microbiota, biology, Cell growth, Fatty Acids, Volatile, biology.organism_classification, Diet, Fructans, Intestines, Disease Models, Animal, FFA2/FFAR2/GPR43, Prebiotics, medicine.anatomical_structure, Liver, Oncology, Biochemistry, chemistry, Cell culture, Cancer cell, cancer cells, Propionate, Metagenome, Female, Propionates |
| الوصف: | BACKGROUND: Metabolites released by the gut microbiota may influence host metabolism and immunity. We have tested the hypothesis that inulin-type fructans (ITF), by promoting microbial production of short-chain fatty acids (SCFA), influence cancer cell proliferation outside the gut. METHODS: Mice transplanted with Bcr-Abl-transfected BaF3 cells, received ITF in their drinking water. Gut microbiota was analysed by 16S rDNA polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) and qPCR. Serum Short-chain fatty acids were quantified by UHPLC-MS. Cell proliferation was evaluated in vivo, by molecular biology and histology, and in vitro. RESULTS: Inulin-type fructans treatment reduces hepatic BaF3 cell infiltration, lessens inflammation and increases portal propionate concentration. In vitro, propionate reduces BaF3 cell growth through a cAMP level-dependent pathway. Furthermore, the activation of free fatty acid receptor 2 (FFA2), a Gi/Gq-protein-coupled receptor also known as GPR43 and that binds propionate, lessens the proliferation of BaF3 and other human cancer cell lines. CONCLUSION: We show for the first time that the fermentation of nutrients such as ITF into propionate can counteract malignant cell proliferation in the liver tissue. Our results support the interest of FFA2 activation as a new strategy for cancer therapeutics. This study highlights the importance of research focusing on gut microbes-host interactions for managing systemic and severe diseases such as leukaemia. |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e508319d0995e109958dfa23d2da6cc3 https://doi.org/10.1038/bjc.2012.409 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e508319d0995e109958dfa23d2da6cc3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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