Issue 4, 2017

Intracellular water – an overlooked drug target? Cisplatin impact in cancer cells probed by neutrons

Abstract

The first neutron scattering study on human nucleated cells is reported, addressing the subject of solvent-slaving to a drug by probing intracellular water upon drug exposure. Inelastic and quasi-elastic neutron scattering spectroscopy with isotope labelling was applied for monitoring interfacial water response to the anticancer drug cisplatin, in the low prognosis human metastatic breast cancer cells MDA-MB-231. Optical vibrational data were also obtained for lyophilised cells. Concentration-dependent dynamical changes evidencing a progressive mobility reduction were unveiled between untreated and cisplatin-exposed samples, concurrent with variations in the native organisation of water molecules within the intracellular medium as a consequence of drug action. The results thus obtained yielded a clear picture of the intracellular water response to cisplatin and constitute the first reported experimental proof of a drug impact on the cytomatrix by neutron techniques. This is an innovative way of tackling a drug's pharmacodynamics, searching for alternative targets of drug action.

Graphical abstract: Intracellular water – an overlooked drug target? Cisplatin impact in cancer cells probed by neutrons

Supplementary files

Article information

Article type
Paper
Submitted
26 Jul 2016
Accepted
23 Nov 2016
First published
24 Nov 2016

Phys. Chem. Chem. Phys., 2017,19, 2702-2713

Intracellular water – an overlooked drug target? Cisplatin impact in cancer cells probed by neutrons

M. P. M. Marques, A. L. M. Batista de Carvalho, V. G. Sakai, L. Hatter and L. A. E. Batista de Carvalho, Phys. Chem. Chem. Phys., 2017, 19, 2702 DOI: 10.1039/C6CP05198G

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