D-ribose acts as trojan horse equilibrating K+ into cancer cells.

Cancer cells have a glycolysis enhancement even in the presence of available oxygen. The “aerobic glycolysis” is known as the Warburg effect and it considered a fundamental metabolic alteration during malignant transformation. The up-regulation of glycolysis in tumour cells is well known and it is the rationale of F18-FDG PET diagnostic technique. This propriety is strictly link to the increase of sugar transporters GLUT in most tumours. Also SGLT family transporters, which include the sodium-glucose symporters, are deregulated in many tumours. The influx of Na+ into tumour cells leads to a change into ions equilibrium, with particular reference to K+ intracellular concentration. We demonstrate that the synergic action of potassium bicarbonate and D-ribose (K:D-Rib) has a cytostatic effect on human cancer cell line (HTB-126), reducing by 30% the doubling population time of treated cancer cells respect to the control, after fourteen days of treatment. The clonogenic assay shows that the colonies formed during the incubation with 5 mM K:D-Rib, are significantly less respect to control but not if fructose is used instead of D-ribose. Cell membranes are permeable to D-ribose that is a carbon source but in contrast to glucose without sodium symport. In addition a significant increase in K+ channel expression, K+ current and /or K+ efflux, can be correlated with tumorigenesis and proliferation. We show that the re-equilibrium of potassium intracellular concentration could be one of the key point to control cancer cell proliferation. Results also report the correlation between morphological cell changes and K+ ion intracellular concentration.