Alasmael, N, Mohan, R, Meira, LB et al. (2 more authors) (2016) Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential. Cancer Letters, 370 (2). pp. 250-259. ISSN 0304-3835
Abstract
Breast cancer is the commonest form of cancer in women, but successful treatment is confounded by the heterogeneous nature of breast tumours: Effective treatments exist for hormone-sensitive tumours, but triple-negative breast cancer results in poor survival. An area of increasing interest is metabolic reprogramming, whereby drug-induced alterations in the metabolic landscape of a tumour slow tumour growth and/or increase sensitivity to existing therapeutics. Nuclear receptors are transcription factors central to the expression of metabolic and transport proteins, and thus represent potential targets for metabolic reprogramming. We show that activation of the nuclear receptor FXR, either by its endogenous ligand CDCA or the synthetic GW4064, leads to cell death in four breast cancer cell lines with distinct phenotypes: MCF-10A (normal), MCF-7 (receptor positive), MDA-MB-231 and MDA-MB-468 (triple negative). Furthermore, we show that the mechanism of cell death is predominantly through the intrinsic apoptotic pathway. Finally, we demonstrate that FXR agonists do not stimulate migration in breast cancer cell lines, an important potential adverse effect. Together, our data support the continued examination of FXR agonists as a novel class of therapeutics for the treatment of breast cancer.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015, Elsevier Ltd. This is an author produced version of a paper published in Cancer Letters. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Apoptosis; Autophagy; Nuclear receptor; Triple negative breast cancer; Bile acids |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 26 Jul 2017 14:53 |
Last Modified: | 30 Jan 2018 19:30 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.canlet.2015.10.031 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:118394 |