Effects of the anticancer agent VM-26 on hexose uptake in Ehrlich cells.
The chemotherapeutic agent VM-26 is a membrane-interactive drug which we have previously demonstrated to be a potent inhibitor of nucleoside transport. Since the carriers mediating nucleoside and hexose transport are structurally and functionally similar, we have further characterized the membrane related properties of this agent by examining its effect on the transport and phosphorylation of hexoses in Ehrlich ascites cells. Under conditions in which only the transport component of hexose uptake was measured, VM-26 had no effect on the influx of 2-deoxyglucose, 3-0-methylglucose, or D-glucose. Glucose-sensitive cytochalasin B binding was only weakly inhibited by the drug. However, VM-26 was an apparent non-competitive inhibitor of the net uptake of 2-deoxyglucose (transport and phosphorylation). Measurement of hexokinase activity in cell extracts failed to demonstrate any significant effect of VM-26 on enzyme activity. In summary, although VM-26 is a potent inhibitor of the transport of nucleosides, it has no apparent effect on the transmembrane flux of hexoses indicating a differential effect on nucleoside and hexose transporters. The ability of the drug to decrease the net accumulation of hexoses in the absence of any detectable effect on hexokinase activity warrants further investigation.
Department of Biochemistry, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC 27103.
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D019325:3-O-Methylglucose; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D003571:Cytochalasin B / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006601:Hexoses / Q000493:pharmacokinetics*; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010766:Phosphorylation; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D013713:Teniposide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D006601:Hexoses; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose; D003571:Cytochalasin B; D013713:Teniposide; D003847:Deoxyglucose; D006593:Hexokinase; D011034:Podophyllotoxin