Poly(ethylene glycol) induces cell toxicity in melanoma cells by producing a hyperosmotic extracellular medium

Poly(ethylene glycol) is a polymer that is widely used as a biomaterial and has been approved in a host of applications. While generally viewed as inert, recent studies with poly(ethylene glycol) suggest that it may have some effects on cells and tissues, making it potentially attractive as a therapeutic agent. In this study, the effect of poly(ethylene glycol) on the cell viability, membrane transport and apoptotic markers of metastatic melanoma cells was examined. The data were combined with observed effects of the polymer on the cell media, including osmolality and viscosity, in order to elucidate any structure-function relationship between the polymer and cells. It was observed that poly(ethylene glycol) reduced the cellular viability of A375 cells, and that the effect was dependent on poly(ethylene glycol) molecular weight and concentration. The mechanism was highly correlated with changes in the osmolality of the cell medium, which is determined by the inherent structure of poly(ethylene glycol), and in particular the ethylene oxide units. This mechanism was specific to poly(ethylene glycol) and was not observed with the similar linear, hydrophilic polymer poly(vinyl pyrrolidone). Overall, the data suggest that poly(ethylene glycol) and poly(ethylene glycol)-like compounds have a distinct effect on cellular activity, presumably mediated in part by their osmotic effects, supporting the further investigation of these polymers as pharmaceutically active compounds.