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Open AccessFeature PaperArticle

Interaction of the Anti-Proliferative GPER Inverse Agonist ERα17p with the Breast Cancer Cell Plasma Membrane: From Biophysics to Biology

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Institut de Biologie Paris-Seine (IBPS), Service de Microscopie éLectronique (IBPS-SME), Sorbonne Université, CNRS, 75005 Paris, France
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Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
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Laboratoire des Biomolécules, LBM, CNRS UMR 7203, Sorbonne Université, Ecole Normale Supérieure, PSL University, 75005 Paris, France
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Institute of Chemistry & Biology of Membranes & Nanoobjects (CBMN), CNRS UMR 5248, Université de Bordeaux, Institut Polytechnique Bordeaux, 33600 Pessac, France
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Cibles Thérapeutiques et Conception de Médicaments (CiTCoM), CNRS UMR 8038, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris Descartes, 75006 Paris, France
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(2), 447; https://doi.org/10.3390/cells9020447 (registering DOI)
Received: 8 November 2019 / Revised: 3 February 2020 / Accepted: 11 February 2020 / Published: 15 February 2020
The peptide ERα17p, which corresponds to the 295-311 fragment of the hinge/AF2 domains of the human estrogen receptor α (ERα), exerts apoptosis in breast cancer cells through a mechanism involving the G protein-coupled estrogen-dependent receptor GPER. Besides this receptor-mediated mechanism, we have detected a direct interaction (Kd value in the micromolar range) of this peptide with lipid vesicles mimicking the plasma membrane of eukaryotes. The reversible and not reversible pools of interacting peptide may correspond to soluble and aggregated membrane-interacting peptide populations, respectively. By using circular dichroism (CD) spectroscopy, we have shown that the interaction of the peptide with this membrane model was associated with its folding into β sheet. A slight leakage of the 5(6)-fluorescein was also observed, indicating lipid bilayer permeability. When the peptide was incubated with living breast cancer cells at the active concentration of 10 μM, aggregates were detected at the plasma membrane under the form of spheres. This insoluble pool of peptide, which seems to result from a fibrillation process, is internalized in micrometric vacuoles under the form of fibrils, without evidence of cytotoxicity, at least at the microscopic level. This study provides new information on the interaction of ERα17p with breast cancer cell membranes as well as on its mechanism of action, with respect to direct membrane effects. View Full-Text
Keywords: apoptotic peptide; lipid vesicles; breast cancer cells; aggregates; membrane interaction; internalization apoptotic peptide; lipid vesicles; breast cancer cells; aggregates; membrane interaction; internalization
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Trichet, M.; Lappano, R.; Belnou, M.; Salazar Vazquez, L.S.; Alves, I.; Ravault, D.; Sagan, S.; Khemtemourian, L.; Maggiolini, M.; Jacquot, Y. Interaction of the Anti-Proliferative GPER Inverse Agonist ERα17p with the Breast Cancer Cell Plasma Membrane: From Biophysics to Biology. Cells 2020, 9, 447.

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