title: 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.
authors.affiliation: Unidade de I&D Química-Física Molecular, Dep. of Chemistry, R. Larga, Univ. Coimbra, 3004-535 Coimbra, Portugal. pmc@ci.uc.pt almbc@ci.uc.pt and Dep. Life Sciences, Univ. Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal.
authors.forename: M P M
authors.identifier: http://orcid.org/0000-0002-8391-0055
authors.initials: MP
authors.lastname: Marques
authors.affiliation: Unidade de I&D Química-Física Molecular, Dep. of Chemistry, R. Larga, Univ. Coimbra, 3004-535 Coimbra, Portugal. pmc@ci.uc.pt almbc@ci.uc.pt.
authors.forename: A L M
authors.identifier: http://orcid.org/0000-0003-1280-3321
authors.initials: AL
authors.lastname: Batista de Carvalho
authors.affiliation: ISIS Facility, STFC Rutherford Appleton Laboratory, Chilton, Didcot, OX 11 0QX, UK.
authors.forename: V Garcia
authors.initials: VG
authors.lastname: Sakai
authors.affiliation: Research Complex at Harwell, STFC Rutherford Appleton Laboratory, Chilton, Didcot, OX 11 0FA, UK.
authors.forename: L
authors.initials: L
authors.lastname: Hatter
authors.affiliation: Unidade de I&D Química-Física Molecular, Dep. of Chemistry, R. Larga, Univ. Coimbra, 3004-535 Coimbra, Portugal. pmc@ci.uc.pt almbc@ci.uc.pt.
authors.forename: L A E
authors.identifier: http://orcid.org/0000-0002-8059-8537
authors.initials: LA
authors.lastname: Batista de Carvalho
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D009502:Neutrons; D013057:Spectrum Analysis; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D014867:Water; D002945:Cisplatin