The Differential Distribution of RAPTA-T in Non-Invasive and Invasive Breast Cancer Cells Correlates with Its Anti-Invasive and Anti-Metastatic Effects

Nanoscale secondary ion mass spectrometry (NanoSIMS) combined with transmission electron microscopy (TEM) can be a powerful approach to visualize the exact distribution of drugs at the sub-cellular level. In this work, we exploit this approach to identify the distribution and localisation of the org...

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Bibliographic Details
Published in:	International journal of molecular sciences 2017-08, Vol.18 (9), p.1869
Main Authors:	Lee, Ronald F S, Escrig, Stéphane, Maclachlan, Catherine, Knott, Graham W, Meibom, Anders, Sava, Gianni, Dyson, Paul J
Format:	Article
Language:	eng
Subjects:	Antineoplastic Agents - administration & dosage Biotechnology Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Membrane - drug effects Cell Nucleolus - drug effects Chemotherapy Chromatin Communication Drug Resistance, Neoplasm - drug effects Electron microscopy Female Humans invasion Mass Spectrometry Mass spectroscopy MCF-7 Cells Metastases Metastasis Neoplasm Invasiveness - pathology Neoplasm Invasiveness - prevention & control Neoplasm Metastasis Nucleoli Organometallic Compounds - administration & dosage Ruthenium Ruthenium compounds Secondary ion mass spectrometry Transmission electron microscopy Tumor cell lines
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Summary:	Nanoscale secondary ion mass spectrometry (NanoSIMS) combined with transmission electron microscopy (TEM) can be a powerful approach to visualize the exact distribution of drugs at the sub-cellular level. In this work, we exploit this approach to identify the distribution and localisation of the organometallic ruthenium(II)-arene drug Ru(η⁶-C₆H₅Me)(pta)Cl₂, termed RAPTA-T, in MDA-MB-231 and MCF-7 human breast cancer cells. These cell lines have been chosen because the former cell lines are highly invasive and resistant to most chemotherapeutic agents and the latter ones are very sensitive to hormonal-based therapies. In the MDA-MB-231 cells, RAPTA-T was found to predominantly localise on the cell membrane and to a lesser extent in the nucleolus. These findings are consistent with the previously reported anti-metastatic properties of RAPTA-T and the observation that once internalized RAPTA-T is associated with chromatin. RAPTA-T shows a lack of membrane accumulation on the non-invasive MCF-7 cells, which correlates well with its selective anti-metastatic properties on invasive cell lines.
ISSN:	1422-0067 1661-6596 1422-0067