The effect of trehalose on intracellular and extracellular nucleotide metabolism. A pilot study

Trehalose is a stable, non-reducing disaccharide, which was found recently to stimulate autophagy, limit the inflammatory response and suppress the growth of specific types of cancer. Purinergic signaling and dysregulation of nucleotide metabolism are the key factors, which play a role in the pathophysiology of cancer development and inflammation. Therefore, this study took a novel approach and aimed to find the effect of trehalose on intracellular, and the extracellular metabolism of nucleotides and NAD + in endothelial and breast cancer cells. The results of this study indicated that in vitro concentrations of trehalose between 0.5 and 5 mM reduced the levels of intracellular NAD + in breast cancer cells. The decrease of intracellular guanosine, independent of GTP energy metabolism, was also observed in both endothelial and cancer cells. Trehalose decreased the activity of ecto-adenosine deaminase. Maximal 3-fold decrease in adenosine deamination was observed in both cell types. Trehalose causes changes in both intracellular and extracellular nucleotide metabolism that is more significant in cancer cells than in endothelium. This effect may have therapeutic potential in cancer and endothelial dysfunction, but its full clarification requires further studies.

Keywords: CD73; Purinergic signaling; eADA; ectonucleotidase; guanosine; trehalose.