title: Statins impair glucose uptake in tumor cells.
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 (18)F-fluorodeoxyglucose ((18)F-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 (18)F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology.
authors.affiliation: Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland.
authors.forename: Agata
authors.initials: A
authors.lastname: Malenda
authors.forename: Anna
authors.initials: A
authors.lastname: Skrobanska
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Issat
authors.forename: Magdalena
authors.initials: M
authors.lastname: Winiarska
authors.forename: Jacek
authors.initials: J
authors.lastname: Bil
authors.forename: Bozenna
authors.initials: B
authors.lastname: Oleszczak
authors.forename: Maciej
authors.initials: M
authors.lastname: Sinski
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Firczuk
authors.forename: Janusz M
authors.initials: JM
authors.lastname: Bujnicki
authors.forename: Justyna
authors.initials: J
authors.lastname: Chlebowska
authors.forename: Adam D
authors.initials: AD
authors.lastname: Staruch
authors.forename: Eliza
authors.initials: E
authors.lastname: Glodkowska-Mrowka
authors.forename: Jolanta
authors.initials: J
authors.lastname: Kunikowska
authors.forename: Leszek
authors.initials: L
authors.lastname: Krolicki
authors.forename: Leszek
authors.initials: L
authors.lastname: Szablewski
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Gaciong
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Koziak
authors.forename: Marek
authors.initials: M
authors.lastname: Jakobisiak
authors.forename: Jakub
authors.initials: J
authors.lastname: Golab
authors.forename: Dominika A
authors.initials: DA
authors.lastname: Nowis
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000096:biosynthesis; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D064847:Multimodal Imaging; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D049268:Positron-Emission Tomography; D060888:Real-Time Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D051272:Glucose Transporter Type 1; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C047515:2-fluoro-2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D002784:Cholesterol; D005947:Glucose