期刊
ONCOTARGET
卷 7, 期 48, 页码 79885-79900出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13089
关键词
toxin; glucosylceramide; lipidomics; intracellular transport; 2-fluoro-2-deoxy-D-glucose
资金
- Norwegian Cancer Society
- Research Council of Norway through its Centres of Excellence funding scheme [179571]
- South-Eastern Norway Regional Health Authority
2-fluoro-2-deoxy-D-glucose (FDG), labeled with F-18 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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