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

• Published in: Physical chemistry chemical physics : PCCP Vol. 19; no. 4; pp. 2702 - 2713
• Main Authors: Marques, M. P. M., Batista de Carvalho, A. L. M., Sakai, V. Garcia, Hatter, L., Batista de Carvalho, L. A. E.
• Format: Journal Article
• Language: English
• Published: England 2017
• Subjects: Cancer; Drugs; Human behavior; Labelling; Monitoring; Neutron scattering; Pharmacology; Physical chemistry
• ISSN: 1463-9076; 1463-9084; 1463-9084
• DOI: 10.1039/C6CP05198G

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.