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Title: Intracellular water - an overlooked drug target? Cisplatin impact in cancer cells probed by neutrons
Authors: Marques, M. P. M. 
Carvalho, A. L. M. Batista de 
Sakai, V Garcia 
Hatter, L 
Carvalho, L. A. E. Batista de 
Issue Date: 25-Jan-2017
Serial title, monograph or event: Physical chemistry chemical physics : PCCP
Volume: 19
Issue: 4
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.
DOI: 10.1039/c6cp05198g
Rights: embargoedAccess
Appears in Collections:FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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