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Intracellular Localization of an Osmocenyl‐Tamoxifen Derivative in Breast Cancer Cells Revealed by Synchrotron Radiation X‐ray Fluorescence Nanoimaging
Author(s) -
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
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201812336
Subject(s) - chemistry , biophysics , fluorescence , intracellular , tamoxifen , mechanism of action , stereochemistry , breast cancer , biochemistry , cancer , medicine , biology , in vitro , physics , quantum mechanics
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.