Cellular effects of fluorodeoxyglucose: Global changes in the lipidome and alteration in intracellular transport
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Simona Kavaliauskiene1,2,3, Maria Lyngaas Torgersen1,2, Anne Berit Dyve Lingelem1,2, Tove Irene Klokk1,2, Tuulia Lintonen4, Helena Simolin4, Kim Ekroos4, Tore Skotland1,2, Kirsten Sandvig1,2,3
1Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway
2Center for Cancer Biomedicine, Oslo University Hospital, Oslo, Norway
3Department of Biosciences, University of Oslo, Oslo, Norway
4Zora Biosciences, Espoo, Finland
Kirsten Sandvig, email: firstname.lastname@example.org
Keywords: Shiga toxin, glucosylceramide, lipidomics, intracellular transport, 2-fluoro-2-deoxy-D-glucose
Received: April 25, 2016 Accepted: October 21, 2016 Published: November 04, 2016
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.
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