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Differential effects and transport kinetics of ascorbate derivatives in leukemic cell lines. 1998

W S Koh, and S J Lee, and H Lee, and C Park, and M H Park, and W S Kim, and S S Yoon, and K Park, and S I Hong, and M H Chung, and C H Park
Department of Medicine, Samsung Medical Center, Kangnam-ku Seoul, Korea.

In order to investigate the differential effects of ascorbate derivatives on leukemic cell growth, we examined their stabilities and transmembrane transport efficiencies. The growth of HL-60 and U937 cells was dose-dependently inhibited by ascorbic acid and sodium ascorbate, but not by dehydroascorbic acid and magnesium ascorbyl 2-phosphate up to 200 microM. The growth-suppression by ascorbic acid was dependent on its redox state, showing a complete or partial reversion by ascorbate oxidase or FeCl3 addition, respectively. Three different patterns of intracellular ascorbic acid accumulation were observed by HPLC according to the species of ascorbate derivative applied for the incubation. Compared with the reduced form of ascorbic acid, the oxidized forms (dehydroascorbic acid, ascorbic acid plus ascorbate oxidase or FeCl3) were rapidly transported into cells and readily degraded, while magnesium ascorbyl 2-phosphate, a stable derivative of ascorbic acid, slowly elevated the intracellular level of ascorbic acid, reaching a plateau at 24 hours. We also measured the differential kinetics of ascorbic acid levels In culture supernatants following the addition of ascorbate derivatives. Ascorbic acid at 40, 10, or 1 microM was observed 3 hours following treatment with 100 microM of ascorbic acid, ascorbic acid plus FeCl3, or magnesium ascorbyl 2-phosphate, respectively. No ascorbic acid was found in the culture supernatant treated with dehydroascorbic acid. This order of ascorbic acid concentrations in culture supernatant reflects their growth-inhibitory effects. Thus the growth inhibitory effect of ascorbic acid appears to be dependent on its concentration in culture medium rather than its intracellular concentration. In conclusion, the results in this study indicate that the differential effects of ascorbate derivatives appear to be due to the actual concentration differences of the reduced form of ascorbic acid in culture medium following their addition, which is determined by their stability and efficiency of cellular uptake.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D007700 Kinetics The rate dynamics in chemical or physical systems.
D002413 Cations, Divalent Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis. Divalent Cations
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D003683 Dehydroascorbic Acid The reversibly oxidized form of ascorbic acid. It is the lactone of 2,3-DIKETOGULONIC ACID and has antiscorbutic activity in man on oral ingestion. Acid, Dehydroascorbic
D005290 Ferric Compounds Inorganic or organic compounds containing trivalent iron. Compounds, Ferric
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001204 Ascorbate Oxidase An enzyme that converts ascorbic acid to dehydroascorbic acid. EC 1.10.3.3. Ascorbase,Ascorbino Dehydrogenase,L-Ascorbate Oxidase,Dehydrogenase, Ascorbino,L Ascorbate Oxidase,Oxidase, Ascorbate,Oxidase, L-Ascorbate
D001205 Ascorbic Acid A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Vitamin C,Ascorbic Acid, Monosodium Salt,Ferrous Ascorbate,Hybrin,L-Ascorbic Acid,Magnesium Ascorbate,Magnesium Ascorbicum,Magnesium di-L-Ascorbate,Magnorbin,Sodium Ascorbate,Acid, Ascorbic,Acid, L-Ascorbic,Ascorbate, Ferrous,Ascorbate, Magnesium,Ascorbate, Sodium,L Ascorbic Acid,Magnesium di L Ascorbate,di-L-Ascorbate, Magnesium

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