Aquaporins in cancer development: opportunities for bioinorganic chemistry to contribute novel chemical probes and therapeutic agents

Abstract

Metal ions and complexes can interfere with the transcellular water flow but also with the cellular transport of glycerol and hydrogen peroxide, via inhibition of the ubiquitous aquaporin channels.

Abstract

Aquaporins (AQPs) are membrane proteins allowing permeation of water, glycerol & hydrogen peroxide across biomembranes, and playing an important role in water homeostasis in different organs, exocrine gland secretion, urine concentration, skin moisturization, fat metabolism and neural signal transduction. Notably, a large number of studies showed that AQPs are closely associated with cancer biological functions and expressed in more than 20 human cancer cell types. Furthermore, AQP expression is positively correlated with tumour types, grades, proliferation, migration, angiogenesis, as well as tumour-associated oedema, rendering these membrane channels attractive as both diagnostic and therapeutic targets in cancer. Recent developments in the field of AQPs modulation have identified coordination metal-based complexes as potent and selective inhibitors of aquaglyceroporins, opening new avenues in the application of inorganic compounds in medicine and chemical biology. The present review is aimed at providing an overview on AQP structure and function, mainly in relation to cancer. In this context, the exploration of coordination metal compounds as possible inhibitors of aquaporins may open the way to novel chemical approaches to study AQP roles in tumour growth and potentially to new drug families. Thus, we describe recent results in the field and reflect upon the potential of inorganic chemistry in providing compounds to modulate the activity of “elusive” membrane targets as the aquaporins.