Cellular effects of fluorodeoxyglucose: Global changes in the lipidome and alteration in intracellular transport.
2-fluoro-2-deoxy-D-glucose (FDG), labeled with 18F radioisotope, is the most common imaging agent used for positron emission tomography (PET) in oncology. However, little is known about the cellular effects of FDG. Another glucose analogue, 2-deoxy-D-glucose (2DG), has been shown to affect many cellular functions, including intracellular transport and lipid metabolism, and has been found to improve the efficacy of cancer chemotherapeutic agents in vivo. Thus, in the present study, we have investigated cellular effects of FDG with the focus on changes in cellular lipids and intracellular transport. By quantifying more than 200 lipids from 17 different lipid classes in HEp-2 cells and by analyzing glycosphingolipids from MCF-7, HT-29 and HBMEC cells, we have discovered that FDG treatment inhibits glucosylceramide synthesis and thus reduces cellular levels of glycosphingolipids. In addition, in HEp-2 cells the levels and/or species composition of other lipid classes, namely diacylglycerols, phosphatidic acids and phosphatidylinositols, were found to change upon treatment with FDG. Furthermore, we show here that FDG inhibits retrograde Shiga toxin transport and is much more efficient in protecting cells against the toxin than 2DG. In summary, our data reveal novel effects of FDG on cellular transport and glycosphingolipid metabolism, which suggest a potential clinical application of FDG as an adjuvant for cancer chemotherapy.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
Simona
S
Kavaliauskiene
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway.
Maria Lyngaas
ML
Torgersen
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway.
Anne Berit Dyve
AB
Lingelem
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway.
Tove Irene
TI
Klokk
Zora Biosciences, Espoo, Finland.
Tuulia
T
Lintonen
Zora Biosciences, Espoo, Finland.
Helena
H
Simolin
Zora Biosciences, Espoo, Finland.
Kim
K
Ekroos
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway.
Tore
T
Skotland
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.|Center for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway.|Department of Biosciences, University of Oslo, Oslo, Norway.
Kirsten
K
Sandvig
D001692:Biological Transport / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects / Q000528:radiation effects; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D019073:HT29 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects* / Q000528:radiation effects; D061986:MCF-7 Cells; D055442:Metabolome / Q000187:drug effects* / Q000528:radiation effects; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D022621:Shiga Toxin / Q000378:metabolism
D019788:Fluorodeoxyglucose F18; D022621:Shiga Toxin
2-fluoro-2-deoxy-D-glucose; Shiga toxin; glucosylceramide; intracellular transport; lipidomics