title: Rhein inhibits glucose uptake in Ehrlich ascites tumor cells by alteration of membrane-associated functions.
abstract: Rhein (RH), 4,5 dihydroxyanthraquinone-2-carboxylic acid, is known to inhibit the glycolysis of neoplastic cells by impairing glucose uptake. In order to establish whether this might be due to a selective interaction of the carrier with the drug or to functional modifications of the cell membrane, the effect of RH on glucose uptake in Ehrlich ascites tumor cells has been investigated. RH strongly inhibits the uptake of both 2-deoxyglucose and 3-O-methylglucose, so the reduced influx therefore cannot be ascribed to an effect on glucose phosphorylation. The inhibition of glucose transport does not depend on a reduction of the number of the carriers as indicated by the inability of the drug to interfere with the synthesis of the transporter. Moreover, the extent of total binding of cytochalasin B, as well as the fact that glucose specificity is not altered, indicate that the intrinsic activity of the glucose carrier is not affected. We therefore conclude that the inhibition of glucose uptake must be ascribed to an interaction of the drug with cell membranes that results in an alteration of membrane-associated functions.
authors.affiliation: Laboratory for Cell Metabolism and Pharmacokinetics, Regina Elena Institute for Cancer Research, Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Castiglione
authors.forename: M
authors.initials: M
authors.lastname: Fanciulli
authors.forename: T
authors.initials: T
authors.lastname: Bruno
authors.forename: M
authors.initials: M
authors.lastname: Evangelista
authors.forename: C
authors.initials: C
authors.lastname: Del Carlo
authors.forename: M G
authors.initials: MG
authors.lastname: Paggi
authors.forename: A
authors.initials: A
authors.lastname: Chersi
authors.forename: A
authors.initials: A
authors.lastname: Floridi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001665:Binding Sites; D015152:Blotting, Northern; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003571:Cytochalasin B / Q000378:metabolism; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005947:Glucose / Q000493:pharmacokinetics*; D006593:Hexokinase / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors; D010766:Phosphorylation; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000880:Anthraquinones; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; D003571:Cytochalasin B; D003847:Deoxyglucose; D009247:NADH, NADPH Oxidoreductases; D006593:Hexokinase; D005947:Glucose; C020491:rhein