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Open AccessArticle

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

1
School of Food Science & Nutrition, University of Leeds, Leeds LS9 7TF, UK
2
School of Medicine, University of Leeds, Leeds LS9 7TF, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(13), 3241; https://doi.org/10.3390/ijms20133241
Received: 13 June 2019 / Revised: 26 June 2019 / Accepted: 27 June 2019 / Published: 2 July 2019
(This article belongs to the Special Issue Liver X Receptors)
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. View Full-Text
Keywords: phytosterols; liver X receptor; transcription; breast cancer; cholesterol; oxysterols phytosterols; liver X receptor; transcription; breast cancer; cholesterol; oxysterols
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Hutchinson, S.A.; Lianto, P.; Moore, J.B.; Hughes, T.A.; Thorne, J.L. Phytosterols Inhibit Side-Chain Oxysterol Mediated Activation of LXR in Breast Cancer Cells. Int. J. Mol. Sci. 2019, 20, 3241.

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