Cancer is still one of the major causes of death despite many years of study and many different research approaches. The theory of Cone [
2] proposes that sustained depolarization of cell membrane is involved in the regulation and control of cell division during both normal and cancerous growth of tissues. Using X-Ray microanalytic method [
3] the correlation between the high Na
+ content and the proliferative cell capacity has been proved in different cell types [
4,
5]. The scope of the present work is to assess the effects of potassium hydrogen carbonate and D-ribose water solution (K:D-Rib) on A72 canine and HTB-126 human cancer cell proliferation. Our previous study [
6] showed the strong antioxidant effect of potassium ascorbate (KAsc) on red blood cell oxidation [
7,
8]. That work [
6] focused on potassium ascorbate which seems to act as a carrier of K
+ inside the cells equilibrating the K
+ inner concentration. Potassium is essential for cell life and it is involved in many different cell pathways. Under physiological condition, K
+ has intracellular concentration of about 150 mM and an extracellular concentration of about 5 mM. Intracellular homeostasis for Na
+ and K
+ is no longer tightly regulated in cancer cells. An alteration of Na
+/K
+ ATPase expression and activity has been shown in patients with cancer [
9,
10]. Epidemiologic evidence suggests that a high K
+ intake inhibits cancer development, and a high Na
+ intake increases the incidence of gastrointestinal malignancies. Studies in human epithelial-derived malignancies indicate that K
+ depletion also occurs, contributing to the increased intracellular Na
+/K
+ ratio [
1]. Na
+/K
+ ATPase uses energy from the hydrolysis of ATP to drive K
+ into cells in exchange for Na
+, which in turn, provides the driving force for the transport of other solutes, notably amino acids, sugars, and phosphates [
10]. It has been found that K
+ is essential to fold and to stabilize G-quadruplex [
11]. Agents that stabilize G-quadruplexes can act as anti-tumour agents, so physiological K
+ concentration is responsible for normal cell behaviour [
12,
13]. Despite these findings, many questions on the key role of K
+ are still not completely clarified, in fact K
+ has a significant role also on apoptotic events [
14].
D-ribose, is a penta-sugar precursor of some amino acids like glutamate, histidine, proline and arginine. D-ribose transformed to piruvate, enters into the Krebs's cycle and has a key role on energetic metabolism; it is also involved in glycogen synthesis. The up-regulation of glycolysis in tumour cells is already well known and it is the rationale of F
18-FDG PET diagnostic technique [
15]. Glucose could be used for energy production through glycolysis, energy storage through glycogen synthesis and for intracellular process through the pentose phosphate pathways (PPP) [
3]. Constitutive up-regulation of glycolysis is also observed even in the presence of adequate oxygen supplies (aerobic glycolysis): a phenomenon first noted by Warburg effect [
16]. D-ribose can be directly synthesized by the non-oxidative transketolase PPP reaction transferring a keto group to glyceraldeyde 3-phoshate from fructose 6-phosphate. Both these substrates are intermediate products of glycolysis.
Because of all this evidence, we started testing the effect of K:D-Rib on A72 cell line proliferation at different concentrations: 5 mM, 0.5 mM, and 0.05 mM. The cell growth is evaluated using MCDI™ software. We move on testing K:D-Rib solution on HTB-126 human cancer cell line. The effect of 5 mM K:D-Rib solution on proliferation and replication capability was valuated with clonogenic assay and counting the number of splitting during 48 days. Preliminary experiments are reported showing the interaction between K:D-Rib and 3-[4,5- dimethylthiazolyl-2]-2,5-diphenyltetrazolium bromide (MTT), which is commonly used to test the cell proliferation and viability.