Intracellular Localization of an Osmocenyl‐Tamoxifen Derivative in Breast Cancer Cells Revealed by Synchrotron Radiation X‐ray Fluorescence Nanoimaging

A series of tamoxifen‐like metallocifens of the group‐8 metals (Fe, Ru, and Os) has strong antiproliferative activity on the triple‐negative breast cancer cells (MDA‐MB‐231). To shed light on the mechanism of action of these molecules, synchrotron radiation X‐ray fluorescence nanoimaging studies wer...

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Published in:Angewandte Chemie International Edition 2019-03, Vol.58 (11), p.3461-3465
Main Authors: Fus, Florin, Yang, Yang, Lee, Hui Zhi Shirley, Top, Siden, Carriere, Marie, Bouron, Alexandre, Pacureanu, Alexandra, da Silva, Julio Cesar, Salmain, Michèle, Vessières, Anne, Cloetens, Peter, Jaouen, Gérard, Bohic, Sylvain
Format: Article
Language:English
Subjects:
bioorganometallic chemistry
Breast cancer
Cancer
Cellular Biology
Chemical Sciences
Coordination chemistry
Electrostatic properties
elemental tomography
Fluorescence
Intracellular
Iron
Life Sciences
Lipophilic
Localization
Mapping
Membranes
Metals
osmium
Radiochemistry
synchrotron
Synchrotron radiation
Tamoxifen
X-ray fluorescence
X-rays
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Summary:A series of tamoxifen‐like metallocifens of the group‐8 metals (Fe, Ru, and Os) has strong antiproliferative activity on the triple‐negative breast cancer cells (MDA‐MB‐231). To shed light on the mechanism of action of these molecules, synchrotron radiation X‐ray fluorescence nanoimaging studies were performed on cells exposed to osmocenyl‐tamoxifen (Oc‐OH‐Tam) to disclose its intracellular distribution. High‐resolution mapping of the lipophilic Oc‐OH‐Tam in cells revealed its preferential accumulation in the endomembrane system. This is consistent with the ability of the amino nitrogen chain of the compounds to be protonated at physiological pH and responsible for electrostatic interactions between Oc‐OH‐Tam and membranes. A comprehensive scenario is proposed that provides new insight into the cellular behavior and activation of Oc‐OH‐Tam and advances the understanding of its mechanism of action. The inner light: Elemental mapping of an osmium anticancer complex in human cancer cells, at pharmacologically relevant concentrations, using a synchrotron X‐ray nanoprobe, reveals an intracellular distribution that encompasses the endomembrane system.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201812336