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EGFR Inhibition by Curcumin in Cancer Cells: A Dual Mode of Action

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Sorbonne Universités, Université de Technologie de Compiègne, CNRS, Laboratoire de Génie Enzymatique et Cellulaire, Rue Roger Couttolenc, CS 60319, F-60203 Compiègne Cedex, France
CNRS; Institut de Pharmacologie et de Biologie Structurale, 205 route de Narbonne, F-31077 Toulouse, France
§ Université de Toulouse, UPS, IPBS, F-31077 Toulouse, France
Sorbonne Universités, Université de Technologie de Compiègne, CNRS, Laboratoire de Biomécanique et Bioingénierie, Rue Roger Couttolenc, CS 60319, F-60203 Compiègne Cedex, France
*Tel.: 0033 3 44 23 45 85. E-mail: [email protected]
Cite this: Biomacromolecules 2015, 16, 5, 1634–1642
Publication Date (Web):April 20, 2015
Copyright © 2015 American Chemical Society

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    Epidermal Growth Factor Receptor (EGFR) is an important target of anticancer therapy. Nowadays, the search for new molecules inhibiting this receptor is turning toward natural substances. One of the most promising natural compounds that have shown an anti-EGFR activity is curcumin, a polyphenol found in turmeric. Its effect on the receptor kinase activity and on the receptor autophosphorylation has been already described, but the mechanism of how curcumin interacts with EGFR is not fully elucidated. We demonstrate that the mode of action of curcumin is dual. This polyphenol is able to inhibit directly but partially the enzymatic activity of the EGFR intracellular domain. The present work shows that curcumin also influences the cell membrane environment of EGFR. Using biomimetic membrane models, we show that curcumin insertion into the lipid bilayer leads to its rigidification. Single particle tracking analyses performed in the membrane of A431 cancer cells confirmed that this effect of curcumin on the membrane slows down the receptor diffusion. This is likely to affect the receptor dimerization and, in turn, its activation.

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    Phosphorylation level of EGFR on Y1068 in A431 cells as a function of EGF exposure time. Surface Plasmon Resonance analysis of curcumin inhibition of the sEGFR binding to immobilized EGF. Frequency histograms of D (log scale), the diffusion coefficient of EGFR as determined from SPT measurements on the A431 cells treated with curcumin. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.5b00229.

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