Human HL-60 myeloid leukemia cells transport dehydroascorbic acid via the glucose transporters and accumulate reduced ascorbic acid.
The cellular accumulation of vitamin C, a substance critical to human physiology, is mediated by transporters located at the cell membrane, and is regulated in a cell-specific manner. Neoplastic cells may have special needs for vitamin C. Therefore, we investigated the transport of vitamin C in a human myeloid leukemia cell line (HL-60). The HL-60 cells lacked the capacity to transport the reduced form of vitamin C, ascorbic acid, but they showed a remarkable ability to transport the oxidized form of vitamin C, dehydroascorbic acid (DHA). Uptake-accumulation studies indicated that the HL-60 cells accumulated ascorbic acid when provided with DHA. Kinetic analysis showed the presence of two functional activities involved in the uptake of DHA, one with low affinity and one with high affinity. Cytochalasin B and phloretin, which inhibit the passage of glucose through the facilitative glucose transporters, also inhibited the transport of DHA by HL-60 cells. Transport of DHA was completed by D- but not L-hexoses, and was sensitive to D-hexose-dependent counter transport acceleration. These data support the concept that HL-60 myeloid leukemic cells transport DHA through the facilitative hexose transporters (glucose transporters) and accumulate the reduced form of ascorbic acid.
Vera
J C
JC
Program in Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Rivas
C I
CI
Zhang
R H
RH
Farber
C M
CM
Golde
D W
DW
D019325:3-O-Methylglucose; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D003683:Dehydroascorbic Acid / Q000378:metabolism*; D003847:Deoxyglucose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D015473:Leukemia, Promyelocytic, Acute; D008757:Methylglucosides / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D010693:Phloretin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose; D003571:Cytochalasin B; D003847:Deoxyglucose; D005947:Glucose; D001205:Ascorbic Acid; D010693:Phloretin; D003683:Dehydroascorbic Acid