Cesium Treatment Depresses Glycolysis Pathway in HeLa Cell.

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.

Cesium suppresses fibroblast proliferation and migration.

During wound healing, fibroblasts proliferate from the margin, and migrate into the provisional matrix where they differentiate into myofibroblasts resulting in wound contraction; however, fibroblasts are hyperproliferative during chronic tissue damage. We previously reported that cesium chloride inhibited a human cancer cell proliferation; therefore, cesium is also presumed to suppress fibroblast proliferation. We here investigated the effects of cesium chloride on the proliferation and migration of murine embryotic fibroblast cells, NIH/3T3 cells. Cultured NIH/3T3 cells with 0-10 mM sodium and cesium chloride were counted using trypan blue dye-exclusion method, then cell growth and viability were evaluated. The percentage of wound closure was calculated by scratch assay. The number of the cells was decreased by application of 1-10 mM cesium in a dose-dependent manner, whereas the viability of the cells was unchanged. The treatment with 3-10 mM cesium inhibited the proliferation rate and % of wound closure compared with controls. These results suggested that cesium inhibits the proliferation and migration of fibroblast cells. This study indicates a possible therapeutic role of cesium chloride in the treatment of wound healing and fibrosis.

Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice.

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine expression is one of the most important targets for the prevention of obesity and improvement of insulin sensitivity. In this study, we have demonstrated that anthocyanin (cyanidin 3-glucoside; C3G) which is a pigment widespread in the plant kingdom, ameliorates hyperglycemia and insulin sensitivity due to the reduction of retinol binding protein 4 (RBP4) expression in type 2 diabetic mice. KK-A(y) mice were fed control or control +0.2% of a C3G diet for 5 weeks. Dietary C3G significantly reduced blood glucose concentration and enhanced insulin sensitivity. The adiponectin and its receptors expression were not responsible for this amelioration. C3G significantly upregulated the glucose transporter 4 (Glut4) and downregulated RBP4 in the white adipose tissue, which is accompanied by downregulation of the inflammatory adipocytokines (monocyte chemoattractant protein-1 and tumor necrosis factor-alpha) in the white adipose tissue of the C3G group. These findings indicate that C3G has significant potency in an anti-diabetic effect through the regulation of Glut4-RBP4 system and the related inflammatory adipocytokines.