ABSTRACT
Effects of water-soluble phenolic antioxidant sodium 3-(3'-tret-butyl-4'-hydroxyphenyl)-propyl thiosulfonate (TS-13), potassium 3,5-dimethyl-4-hydroxybenzyl thioetanoate (BEP-11-K) and potassium 3-(3',5'-ditretbutyl-4'-hydroxyphenyl)-propionate (potassium phenosan) on tumor cells proliferative activity and the role of redox-dependent and calcium-dependent signaling mechanisms in realization of tumor cell response to the antioxidant action were studied. Potassium phenosan and BEP-11-K were found to stimulate proliferation and ARE-inducing phenolic antioxidant TS-13 was found to inhibit tumor cell growth in culture. The tumor cell growth rate depended on the rate of intracellular reactive oxygen species production and was decreased by apocynin (a NADPH-oxidase inhibitor) and antimycin A (an ubiquinol-cytochrome c oxidoreductase inhibitor). TS-13 action on tumor cells was accompanied by a transient increase in intracellular reactive oxygen species production and the intracellular calcium concentration, whereas cell incubation with potassium phenosan and BEP-11-K did not influence the reactive oxygen species level and intracellular calcium ions. Cyclosporine A blocked the inhibitory effect of TS-13. Thus, it can be reasonably speculated that phenolic antioxidant TS-13 starts mitochondria-dependent apoptosis in tumor cells by the opening of permeability transition pores.
Subject(s)
Antioxidants/pharmacology , Apoptosis/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Mitochondria/metabolism , Response Elements , Thiosulfonic Acids/pharmacology , Cell Line, Tumor , Humans , Mitochondria/pathology , NADPH Oxidases/antagonists & inhibitors , NADPH Oxidases/metabolism , Neoplasm Proteins/antagonists & inhibitors , Neoplasm Proteins/metabolism , Neoplasms , Reactive Oxygen Species/metabolismABSTRACT
A model for the redox regulation of the functional state of the cell has been constructed on the basis of representation of electron transfer processes by equivalent electric circuits. The mechanism of action of redox active molecules on biosystems has been discussed in terms of circuit theory. A method for determining the parameters of cellular redox sensors has been proposed. It has been established that the concentration and redox potential of compounds entering the cell are the main regulatory parameters of redox signals for the cell. It has been experimentally shown that the calcium response to hydrogen peroxide in rat C6 glioma cells and human FL amnion cells depends on the redox buffer capacity of cells.
Subject(s)
Calcium Signaling/drug effects , Hydrogen Peroxide/pharmacology , Models, Biological , Oxidants/pharmacology , Oxidative Stress/drug effects , Animals , Cell Line, Tumor , Humans , Oxidation-Reduction/drug effects , RatsABSTRACT
The parameters of the acid-base state and redox state of erythrocytes have been studied with the use of the fluorescent probes 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein and 2',7'-dichlorodihydrofluorescein. It has been found that the value of redox state parameters in erythrocytes depends both on the extracellular and intracellular concentrations of hydrogen ions. It has been shown that hydrogen peroxide induces a decrease in the value of the intracellular pH. The interrelation of cellular homeostasis parameters characterizing the acid-base and redox states of erythrocytes has been theoretically and experimentally substantiated.
Subject(s)
Erythrocytes/chemistry , Fluorescent Dyes/chemistry , Hydrogen/chemistry , Cations, Monovalent/chemistry , Humans , Hydrogen-Ion Concentration , Oxidation-ReductionABSTRACT
Effects of ascorbic acid on calcium homeostasis of human laryngeal carcinoma cells were studied. Intracellular concentration of free calcium and intracellular pH were measured by fluorescent analysis. Ascorbic acid in concentrations of 3-10 mM caused pH drop and sharply increased concentrations of free Ca ions in HEp-2 cells. Intracellular concentration of free Ca ions resulted from Ca ion release from the thapsigargin-sensitive Ca depots.
Subject(s)
Antioxidants/pharmacology , Ascorbic Acid/pharmacology , Calcium Signaling/drug effects , Calcium/metabolism , Carcinoma/drug therapy , Laryngeal Neoplasms/drug therapy , Antioxidants/administration & dosage , Ascorbic Acid/administration & dosage , Carcinoma/metabolism , Cell Line, Tumor , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Extracellular Space/drug effects , Fluorescence , Humans , Hydrogen Peroxide/pharmacology , Hydrogen-Ion Concentration , Intracellular Space/drug effects , Intracellular Space/metabolism , Laryngeal Neoplasms/metabolism , Oxidants/pharmacology , Thapsigargin/pharmacology , Time FactorsABSTRACT
The introduction of the parameters characterizing the redox state of the cell, such as the effective redox potential and the redox buffer capacity has been theoretically substantiated. A comparative study of the parameters of the redox state of erythrocytes from healthy donors and patients with diabetes and acute coronary syndrome has been performed. It was found that the redox buffer capacity in erythrocytes from patients with diabetes and acute coronary syndrome was reduced by 30-40% in comparison with the redox buffer capacity of erythrocytes from healthy donors. The largest change in the effective redox potential was observed for erythrocytes from patients with diabetes, which indicates a more expressed oxidative stress in this pathology.
