Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2151506 | Neoplasia | 2012 | 13 Pages |
Abstract
Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at neither transcriptional nor protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered 18F-fluorodeoxyglucose (18F-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting 18F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology.
Keywords
GLUT2-DOG2-DeoxyglucosePBMCCRACMβCD18F-FDGFPPPET/CTMevalonic acidcholesterol recognition/interaction amino acid consensuspositron emission tomography/computed tomographyGlucose transportercluster of differentiationPeripheral blood mononuclear cellfarnesyl pyrophosphateSUVmethyl-β-cyclodextrinstandardized uptake valuehemagglutinin
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Authors
Agata Malenda, Anna Skrobanska, Tadeusz Issat, Magdalena Winiarska, Jacek Bil, Bozenna Oleszczak, Maciej Sinski, MaÅgorzata Firczuk, Janusz M. Bujnicki, Justyna Chlebowska, Adam D. Staruch, Eliza Glodkowska-Mrowka, Jolanta Kunikowska, Leszek Krolicki,