Intracellular water as a mediator of anticancer drug action

Abstract

ABSTRACT Water is the major constituent of the human body and plays a vital role in biochemical processes. Even subtle variations in the structure or dynamics of intracellular water may be the driving force for disrupting homeostasis in the highly crowded intracellular milieu, which in turn may trigger biomolecular dysfunction eventually leading to cell death. This article highlights several studies on human cells and DNA, that establish intracellular water as a key mediator of cytotoxicity. Inelastic and quasi-elastic neutron scattering techniques were applied, which provide a direct probe, at the atomic scale, of the behaviour of both cytoplasmic and hydration water, in the presence and absence of drugs. While the primary targets of drugs are biological receptors, we propose water as a potential secondary target for chemotherapy. The methodology presented constitutes an innovative approach for chemotherapeutic research. In addition, it showcases the value of neutron spectroscopy, a traditionally physico-chemical tool, for clinically-relevant research.