Intracellular Localization of an Osmocenyl-Tamoxifen Derivative in Breast Cancer Cells Revealed by Synchrotron Radiation X-ray Fluorescence Nanoimaging.
Florin FusYang YangHui Zhi Shirley LeeSiden TopMarie CarriereAlexandre BouronAlexandra PacureanuJulio Cesar da SilvaMichèle SalmainAnne VessièresPeter CloetensGérard JaouenSylvain BohicPublished in: Angewandte Chemie (International ed. in English) (2019)
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.
Keyphrases
- breast cancer cells
- high resolution
- induced apoptosis
- cell cycle arrest
- energy transfer
- mass spectrometry
- estrogen receptor
- cell death
- endoplasmic reticulum stress
- oxidative stress
- signaling pathway
- reactive oxygen species
- dual energy
- single cell
- climate change
- radiation therapy
- risk assessment
- radiation induced
- cell proliferation
- high speed
- health risk
- aqueous solution
- electron microscopy
- contrast enhanced