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Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells

Low fruit and vegetable consumption and high saturated fat consumption causes elevated circulating cholesterol and are breast cancer risk factors. During cholesterol metabolism, oxysterols form that bind and activate the liver X receptors (LXRs). Oxysterols halt breast cancer cell proliferation but...

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Autores principales: Hutchinson, Samantha A., Lianto, Priscilia, Moore, J. Bernadette, Hughes, Thomas A., Thorne, James L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651815/
https://www.ncbi.nlm.nih.gov/pubmed/31269628
http://dx.doi.org/10.3390/ijms20133241
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author Hutchinson, Samantha A.
Lianto, Priscilia
Moore, J. Bernadette
Hughes, Thomas A.
Thorne, James L.
author_facet Hutchinson, Samantha A.
Lianto, Priscilia
Moore, J. Bernadette
Hughes, Thomas A.
Thorne, James L.
author_sort Hutchinson, Samantha A.
collection PubMed
description Low fruit and vegetable consumption and high saturated fat consumption causes elevated circulating cholesterol and are breast cancer risk factors. During cholesterol metabolism, oxysterols form that bind and activate the liver X receptors (LXRs). Oxysterols halt breast cancer cell proliferation but enhance metastatic colonization, indicating tumour suppressing and promoting roles. Phytosterols and phytostanols in plants, like cholesterol in mammals, are essential components of the plasma membrane and biochemical precursors, and in human cells can alter LXR transcriptional activity. Here, a panel of breast cancer cell lines were treated with four dietary plant sterols and a stanol, alone or in combination with oxysterols. LXR activation and repression were measured by gene expression and LXR-luciferase reporter assays. Oxysterols activated LXR in all cell lines, but surprisingly phytosterols failed to modulate LXR activity. However, phytosterols significantly inhibited the ability of oxysterols to drive LXR transcription. These data support a role for phytosterols in modulating cancer cell behaviour via LXR, and therefore suggest merit in accurate dietary recordings of these molecules in cancer patients during treatment and perhaps supplementation to benefit recovery.
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spelling pubmed-66518152019-08-08 Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells Hutchinson, Samantha A. Lianto, Priscilia Moore, J. Bernadette Hughes, Thomas A. Thorne, James L. Int J Mol Sci Article Low fruit and vegetable consumption and high saturated fat consumption causes elevated circulating cholesterol and are breast cancer risk factors. During cholesterol metabolism, oxysterols form that bind and activate the liver X receptors (LXRs). Oxysterols halt breast cancer cell proliferation but enhance metastatic colonization, indicating tumour suppressing and promoting roles. Phytosterols and phytostanols in plants, like cholesterol in mammals, are essential components of the plasma membrane and biochemical precursors, and in human cells can alter LXR transcriptional activity. Here, a panel of breast cancer cell lines were treated with four dietary plant sterols and a stanol, alone or in combination with oxysterols. LXR activation and repression were measured by gene expression and LXR-luciferase reporter assays. Oxysterols activated LXR in all cell lines, but surprisingly phytosterols failed to modulate LXR activity. However, phytosterols significantly inhibited the ability of oxysterols to drive LXR transcription. These data support a role for phytosterols in modulating cancer cell behaviour via LXR, and therefore suggest merit in accurate dietary recordings of these molecules in cancer patients during treatment and perhaps supplementation to benefit recovery. MDPI 2019-07-02 /pmc/articles/PMC6651815/ /pubmed/31269628 http://dx.doi.org/10.3390/ijms20133241 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hutchinson, Samantha A.
Lianto, Priscilia
Moore, J. Bernadette
Hughes, Thomas A.
Thorne, James L.
Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells
title Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells
title_full Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells
title_fullStr Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells
title_full_unstemmed Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells
title_short Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells
title_sort phytosterols inhibit side-chain oxysterol mediated activation of lxr in breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651815/
https://www.ncbi.nlm.nih.gov/pubmed/31269628
http://dx.doi.org/10.3390/ijms20133241
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