Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models

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dc.contributor.author Phelan, John P.
dc.contributor.author Reen, F. Jerry
dc.contributor.author Dunphy, Niall
dc.contributor.author O'Connor, Rosemary
dc.contributor.author O'Gara, Fergal
dc.date.accessioned 2016-10-18T09:10:17Z
dc.date.available 2016-10-18T09:10:17Z
dc.date.issued 2016-07-14
dc.identifier.citation Phelan, J.P., Reen, F.J., Dunphy, N., O’Connor, R. and O’Gara, F. (2016) 'Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models', BMC Cancer, 16(1), 476 (12 pp.). doi: 10.1186/s12885-016-2528-2 en
dc.identifier.volume 16 en
dc.identifier.issued 1 en
dc.identifier.issn 1471-2407
dc.identifier.uri http://hdl.handle.net/10468/3190
dc.identifier.doi 10.1186/s12885-016-2528-2
dc.description.abstract BACKGROUND: The role of the microbiome has become synonymous with human health and disease. Bile acids, as essential components of the microbiome, have gained sustained credibility as potential modulators of cancer progression in several disease models. At physiological concentrations, bile acids appear to influence cancer phenotypes, although conflicting data surrounds their precise physiological mechanism of action. Previously, we demonstrated bile acids destabilised the HIF-1α subunit of the Hypoxic-Inducible Factor-1 (HIF-1) transcription factor. HIF-1 overexpression is an early biomarker of tumour metastasis and is associated with tumour resistance to conventional therapies, and poor prognosis in a range of different cancers. METHODS: Here we investigated the effects of bile acids on the cancer growth and migratory potential of cell lines where HIF-1α is known to be active under hypoxic conditions. HIF-1α status was investigated in A-549 lung, DU-145 prostate and MCF-7 breast cancer cell lines exposed to bile acids (CDCA and DCA). Cell adhesion, invasion, migration was assessed in DU-145 cells while clonogenic growth was assessed in all cell lines. RESULTS: Intracellular HIF-1α was destabilised in the presence of bile acids in all cell lines tested. Bile acids were not cytotoxic but exhibited greatly reduced clonogenic potential in two out of three cell lines. In the migratory prostate cancer cell line DU-145, bile acids impaired cell adhesion, migration and invasion. CDCA and DCA destabilised HIF-1α in all cells and significantly suppressed key cancer progression associated phenotypes; clonogenic growth, invasion and migration in DU-145 cells. CONCLUSIONS: These findings suggest previously unobserved roles for bile acids as physiologically relevant molecules targeting hypoxic tumour progression. en
dc.description.sponsorship Science Foundation Ireland (SSPC-2, 12/RC/2275; 13/TIDA/B2625; 12/TIDA/B2411; 12/TIDA/B2405; 14/TIDA/2438); Department of Agriculture and Food (FIRM/RSF/CoFoRD; FIRM 08/RDC/629; FIRM 1/F009/MabS; FIRM 13/F/516); Irish Research Council for Science, Engineering and Technology (PD/2011/2414; GOIPG/2014/647); Health Research Board/Irish Thoracic Society (MRCG-2014-6); Marine Institute (Beaufort award C2CRA 2007/082); Teagasc (Walsh Fellowship 2013) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher BioMed Central en
dc.rights © 2016, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Bile acids en
dc.subject Cancer models en
dc.subject Dimethyloxaloglycine (DMOG) en
dc.subject HIF-1 transcription factor en
dc.subject HIF-1α subunit en
dc.subject Hypoxia en
dc.title Bile acids destabilise HIF-1α and promote anti-tumour phenotypes in cancer cell models en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Fergal O’Gara, Microbiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: f.ogara@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Department of Agriculture, Food and the Marine en
dc.contributor.funder Irish Research Council for Science, Engineering and Technology en
dc.contributor.funder Health Research Board en
dc.contributor.funder Marine Institute en
dc.contributor.funder Teagasc en
dc.contributor.funder Seventh Framework Programme en
dc.description.status Peer reviewed en
dc.identifier.journaltitle BMC Cancer en
dc.internal.IRISemailaddress f.ogara@ucc.ie
dc.identifier.articleid 476
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/607786/EU/BluePharmTrain/BLUEPHARMTRAIN en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/312184/EU/Increasing Value and Flow in the Marine Biodiscovery Pipeline/PHARMASEA en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/311975/EU/Marine Microorganisms: Cultivation Methods for Improving their Biotechnological Applications/MACUMBA en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP1::KBBE/287589/EU/Marine Microbial Biodiversity, Bioinformatics and Biotechnology/MICRO B3 en
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/256596/EU/Dissecting the role of a novel transcriptional regulator in microbial-host interactomes./MEXT REGULATION en


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© 2016, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Except where otherwise noted, this item's license is described as © 2016, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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