Cesium Treatment Depresses Glycolysis Pathway in HeLa Cell

Abstract

Background/Aims: Cesium (Cs) is an alkali metal element that is of no essential use for humans; it has no known beneficial function that is verified by clinical research. When used as an alternative cancer therapy, it even causes toxicity in high doses. Thus, before using Cs as treatment in clinical settings, it is important to clearly determine its biological effects on cells. However, Cs was found to suppress the proliferation of human cervical cancer cells in a dose-dependent manner, and it was assumed that Cs inhibits the glycolysis pathway. In this study, we clearly determined the step of the glycolysis pathway that is affected by Cs. Methods: The glycolytic enzyme expressions, activities, and metabolite concentrations in HeLa cells were measured by PCR, western blotting, and enzymatic methods, after treating the cells with Cs for 3 days. Results: Cs treatment decreased transcriptional and expression levels of hexokinase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase (PK), and lactate dehydrogenase and the activity of PK. Analysis of glycolysis pathway metabolites revealed that Cs treatment reduces lactate level and increases the level of nicotinamide adenine dinucleotide (oxidized form, NAD+); however, it did not affect the levels of pyruvate and nicotinamide adenine dinucleotide (reduced form, NADH). Increase of the [NAD+]/[NADH] ratio and decrease of the [lactate]/[pyruvate] ratio indicate that Cs treatment inhibits the aerobic glycolysis pathway. Conclusion: Cs treatment inhibits PK activity and increases the [NAD+]/[NADH] ratio. Hence, Cs has been determined to inhibit glycolysis, especially the aerobic glycolysis pathway. These results suggest that suppression of HeLa cell proliferation following Cs treatment was caused by inhibition of aerobic glycolysis by Cs.

Ecological and toxicological features of the effect of stable cesium on striated muscle tissue (myocardium and skeletal muscles) of mammals

“…Like potassium, cesium is intensively absorbed in the small intestine and excreted by the distal part of the nephron (Lyon & Mayhew, 2003). Absorption of cesium is associated with the depletion of both intracellular and extracellular potassium and is accompanied by the occurrence of cesium-associated hypokalemia (Horn et al, 2015;Kobayashi et al, 2021).…”

“…Side effects of Cs include QT prolongation, hypokalemia, seizures, cardiac arrhythmia (torsades de pointes), syncope, and cardiac arrest. However, some patients treated with various doses of Cs have been reported to remain alive for 10-150 days and some others for up to one year (Kobayashi et al, 2017;Kobayashi et al, 2021).…”

“…An increase and a decrease in the intracellular concentrations of cesium and potassium are respectively observed in cells treated with cesium, inducing an intracellular cation imbalance, and an intracellular pH shift towards alkalosis is observed. A decrease in the concentration of potassium ions leads to a decrease in the activity of the glycolytic enzyme pyruvate kinase which uses K + as a cofactor that leads to an energy deficit in cells (Kobayashi et al, 2017;Kobayashi et al, 2021). The study of the effect of cesium cations on glycine receptors (GlyRs), which are one of the most widely distributed neurotransmitter receptors in the peripheral and central nervous systems, revealed an agonistic interaction with GlyRs (Fricke et al, 2023).…”

The Toxicological Analysis and Toxicological Risk Assessment of Chosen Elemental Impurities (Ag, Au, Co, Cr, Cs, Li, Mo, Se, and Sr) in Green Tea (Camellia sinensis (L.)) Infusions

“…Caesium side symptoms include cardiac arrhythmias, hypokalaemia, fainting, convulsions, and cardiac arrest. There is no complete understanding of caesium functions [ 32 ]. Lithium is another engaging element that is used as a therapeutic agent for humans.…”

The Control of Novel and Traditional Elemental Impurities: Ag, Au, Co, Cs, Li, Mo, Se, Sr, and V in Mint Tea Infusions (Peppermint, Mentha piperita L.) Available in Poland: A Health Risk Assessment

“…Cesium is an interesting but underestimated element because natural Cs exist mainly as 133 Cs, and is also slightly inclusive of the other eleven main radioactive isotopes that can be noxious to humans [ 21 ]. Cesium toxicity is dose-dependent but full knowledge of its acute and chronic toxicity is not available, Cs side effects include hypokalaemia, seizures, cardiac arrhythmias, syncope and cardiac arrest [ 22 ]. The justifications for choosing these EI were: Health risk assessment of new and traditional EI (Ag, Au, Co, Cs, Li, Mo, Se, Sr, and V) for the first time in mint tea infusions ( Mentha piperita L.) available in Polish markets; EI profile in mint tea infusions (µg/L of infusion) as raw results; Estimation of the weekly intake (µg/L of infusion/week) established on weekly tea consumption (based on [ 23 ]); Estimation of the weekly intake per body weight (µg/L of infusion/week/bw) based on weekly tea consumption per individual (~70 kg bw) in comparison to the Provisional Tolerable Weekly Intake (PTWI) appointed by the Joint FAO/WHO Expert Committee on Food Additives (JECFA); and Individual health risk assessment for elements without PTWI values.…”