RHEIN INHIBITS GLUCOSE-UPTAKE IN EHRLICH ASCITES TUMOR-CELLS BY ALTERATION OF MEMBRANE-ASSOCIATED FUNCTIONS

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 inter action of the carrier with the drug or to functional modifications of the cell membrane, the effect of RH on glucose uptake in Ehrlich ascit es tumor cells has been investigated. RH strongly inhibits the uptake of both 2-deoxyglucose and 3-O-methylglucose, so the reduced influx th erefore cannot be ascribed to an effect on glucose phosphorylation. Th e inhibition of glucose transport does not depend on a reduction of th e 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 s pecificity is not altered, indicate that the intrinsic activity of the glucose carrier is not affected. We therefore conclude that the inhib ition of glucose uptake must be ascribed to an interaction of the drug with cell membranes that results in an alteration of membrane-associa ted functions.