title: Intracellular accumulation of ascorbic acid is inhibited by flavonoids via blocking of dehydroascorbic acid and ascorbic acid uptakes in HL-60, U937 and Jurkat cells.
abstract: In HL-60, U937 and Jurkat cells, the intracellular accumulation of ascorbic acid occurred via uptakes of both dehydroascorbic acid (an oxidized metabolite of ascorbic acid) and ascorbic acid (vitamin C). Dehydroascorbic acid and ascorbic acid were transported into cells by sodium-independent glucose transporters (GLUT 1 and GLUT 3) and sodium-dependent ascorbic acid transporters, respectively. Flavonoids inhibited the intracellular accumulation of ascorbic acid by blocking dehydroascorbic acid and ascorbic acid uptakes in the transformed cells. At flavonoid concentrations of 10-70 micromol/L, approximately 50% of dehydroascorbic acid uptake was inhibited in the cells. In Jurkat cells, two potent flavonoids (myricetin and quercetin) competitively inhibited dehydroascorbic acid uptake, and K(i) values were approximately 14 and 15 micromol/L, respectively. Because GLUT 1 and GLUT 3 transport dehydroascorbic acid, the inhibition of dehydroascorbic acid uptake by flavonoids was investigated by using Chinese hamster ovary cells overexpressing rat GLUT 1 or human GLUT 3. Myricetin at concentrations of 22 and 18 micromol/L, respectively, inhibited half of dehydroascorbic acid uptake in the cells overexpressing GLUT 1 and GLUT 3. Myricetin also inhibited ascorbic acid uptake; inhibition was noncompetitive with K(i) = 14 micromol/L in Jurkat cells. These data indicate that flavonoids inhibit both ascorbic acid and dehydroascorbic acid uptake but do so by different mechanisms. These data may contribute to new understanding of the biological effect of flavonoids on the intracellular accumulation of ascorbic acid in human cells.
authors.affiliation: Phytonutrients Laboratory, BHNRC, ARS, U.S. Department of Agriculture, Beltsville 20705, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Park
authors.forename: M
authors.initials: M
authors.lastname: Levine
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D016466:CHO Cells; D006224:Cricetinae; D003683:Dehydroascorbic Acid / Q000378:metabolism* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005419:Flavonoids / Q000494:pharmacology*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D020298:U937 Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D005419:Flavonoids; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; C040015:myricetin; D011794:Quercetin; D001205:Ascorbic Acid; D003683:Dehydroascorbic Acid