Potassium bicarbonate and D-ribose effects on A72 canine and HTB-126 human cancer cell line proliferation in vitro

Abstract

BackgroundThe synergic action of KHCO3 and D-ribose is tested on A72 and HTB-126 cell lines proliferation using K:D-Rib solution. Altered Na+/K+ ATPase expression and activity were shown in patients with cancer. Studies in human epithelial-derived malignancies indicate that K+ depletion also occurs, contributing to the increased intracellular Na+/K+ ratio [1]. D-ribose transformed to piruvate, enters into the Krebs's cycle and has a key role on energetic metabolism. The up-regulation of glycolysis in tumor cells is already well known and it is the rationale of F18-FDG PET diagnostic technique. D-ribose is synthesized by the non-oxidative transketolase PPP reaction.ResultsResults with different K:D-Rib concentrations show that MTT salt interferes with K:D-Rib solution and therefore this method is not reliable. The UV/VIS measurements show that K:D-Rib solutions reduce MTT salt to formazan in absence of cells. Cell proliferation has then been evaluated analysing the digital photos of the Giemsa stained cells with MCID™ software. At 5 mM K:D-Rib concentration, the cell growth arrests between 48 h and 72 h; in fact the cell number after 48 h is around the same with respect to the control after 72 h. In case of HTB-126 human cancer cells, the growth rate was valuated counting the splitting times during 48 days: control cells were split sixteen times while 5 mM treated cells eleven times. Most relevant, the clonogenic assay shows that nine colonies are formed in the control cells while only one is formed in the 5 mM and none in 10 mM treated cells.ConclusionsThe K:D-Rib solution has an antioxidant behaviour also at low concentrations. Incubation with 5 mM K:D-Rib solution on A72 cells shows a cytostatic effect at 5 mM, but it needs more than 24 h of incubation time to evidence this effect on cell proliferation. At the same concentration on human HTB-126 cells, K:D-Rib solution shows a clear replication slowing but the cytostatic effect at 10 mM K:D-Rib solution only. Results on A72 cells indicate the K+ uptake could be determinant either to arrest or to slow down cell growth.

Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

“…Previous studies have revealed that hybrid-type intramolecular G-quadruplexes appear to be the predominant conformation formed in human telomeric sequences in solution in the presence of K + (72,73). It has been reported that the increase of K + transported into the cells alters the shape of G-quadruplexes (30). Therefore, the time-dependent effect observed in the present study upon treatment with A and K may reflect the time required for G-quadruplexes in tumor cells to shift from the Na + to the K + form.…”

“…This mechanism causes the release of calcium from its intracellular deposits and a simultaneous increase in glucose uptake, thus enhancing mitogenic stimulation (27,56,57). It has been previously demonstrated that the administration of K ascorbate produced anticancer effects in vitro (30,58), possibly due to the carrier properties of A, which allows a rapid diffusion of K into the cells, leading to the inhibition of tumor cell proliferation (27,30).…”

“…Previous studies reported a strong antioxidant effect of K ascorbate on red blood cell oxidation (28,29). In addition, it has been suggested that K ascorbate may act as a K intracellular carrier and may be able to inhibit the cell cycle in tumor cells (30).…”

K-D:rib dampens Hs 578T cancer cell chemoinvasion and proliferation

“…Our most recent work demonstrates that the 5 mM K:D-rib solution slows the replication of the Hs 578T cell line and has a cytostatic effect on canine carcinoma cell line (A72) [ 11 ]. The effects of potassium ascorbate together with D-ribose have been investigated on Beckwith - Wiedemann syndrome and in a case of Prader Willi syndrome and Costello syndrome, severe syndromes characterized both by a high oncological risk and by high ROS concentration [ 12 ]–[ 14 ].…”

K-D:rib dampens Hs 578T cancer cell chemoinvasion and proliferation

“…Our most recent work demonstrates that the 5 mM K: D-rib solution slows the replication of the Hs 578T cell line and has a cytostatic effect on canine carcinoma cell line (A72) [11]. The effects of potassium ascorbate together with D-ribose have been investigated on BeckwithWiedemann syndrome and in a case of Prader Willi syndrome and Costello syndrome, severe syndromes characterized both by a high oncological risk and by high ROS concentration [12][13][14].…”