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Int. J. Mol. Sci. 2017, 18(9), 1869; doi:10.3390/ijms18091869

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

1
Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland
2
Laboratory for Biological Geochemistry, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
3
Interdisciplinary Centre for Electron Microscopy, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
4
Center for Advanced Surface Analysis, Institute of Earth Sciences, University of Lausanne, CH-1015 Lausanne, Switzerland
5
Callerio Foundation Onlus, via A. Fleming 22, 34127 Trieste, Italy
*
Author to whom correspondence should be addressed.
Received: 27 July 2017 / Revised: 22 August 2017 / Accepted: 24 August 2017 / Published: 29 August 2017
(This article belongs to the Special Issue Chemical and Molecular Approach to Tumor Metastases)
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Abstract

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. View Full-Text
Keywords: breast cancer; invasion; metastasis; ruthenium breast cancer; invasion; metastasis; ruthenium
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lee, R.F.S.; Escrig, S.; Maclachlan, C.; Knott, G.W.; Meibom, A.; Sava, G.; Dyson, P.J. The Differential Distribution of RAPTA-T in Non-Invasive and Invasive Breast Cancer Cells Correlates with Its Anti-Invasive and Anti-Metastatic Effects. Int. J. Mol. Sci. 2017, 18, 1869.

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