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Molecules 2018, 23(8), 1992; https://doi.org/10.3390/molecules23081992

Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple-Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha

Bio-Pharmaceutical Chemistry and Molecular Pharmacology, Faculty of Applied Natural Sciences, Technische Hochschule Koeln, Chempark, 51373 Leverkusen, Germany
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Received: 12 July 2018 / Revised: 7 August 2018 / Accepted: 8 August 2018 / Published: 10 August 2018
(This article belongs to the Special Issue Bioactive Molecules and Their Mechanisms of Action)
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Abstract

Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a variety of promising biological activities, including potent anti-inflammatory effects. However, few studies examined pseudopterosin in the treatment of cancer cells and, to our knowledge, the ability to inhibit triple-negative breast cancer (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as-yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell proliferation after knocking down glucocorticoid receptor α (GRα) revealed that the antiproliferative effects of pseudopterosin were significantly inhibited when GRα expression was reduced. Furthermore, pseudopterosin inhibited the invasion of MDA-MB-231 3D tumor spheroids embedded in an extracellular-like matrix. Remarkably, the knockdown of GRα in 3D tumor spheroids revealed increased ability of cells to invade the surrounding matrix. In a coculture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB-231 cells, and the production of interleukin 6 (IL-6) and interleukin 8 (IL-8) significantly increased compared to a monoculture. Notably, pseudopterosin indicated to block cytokine elevation, representing key players in tumor progression in the coculture. Thus, our results reveal pseudopterosin treatment as a potential novel approach in TNBC therapy. View Full-Text
Keywords: pseudopterosin; triple-negative breast cancer; glucocorticoid receptor alpha; dexamethasone; cell proliferation; 3D invasion; tumor spheroid; coculture; interleukin 6; interleukin 8 pseudopterosin; triple-negative breast cancer; glucocorticoid receptor alpha; dexamethasone; cell proliferation; 3D invasion; tumor spheroid; coculture; interleukin 6; interleukin 8
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Sperlich, J.; Teusch, N. Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple-Negative Breast Cancer by Agonizing Glucocorticoid Receptor Alpha. Molecules 2018, 23, 1992.

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