Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

PURPOSE: Glycogen synthase kinase 3 (GSK3) is a key controlling element of many cellular processes including cell-cycle progression and recent studies suggest that GSK3 is a potential anticancer target. Changes in glucose metabolism associated with GSK3 inhibition may impact on lipid synthesis, whilst lipid metabolites can act as molecular response markers. METHODS: Here, SKBr3 breast and HCT8 colorectal cancer cells were treated with the GSK3 inhibitor SB216763, and [14C (U)] glucose and [3H] choline incorporation into lipids was determined. Cell extracts from treated cells were subject to 31P NMR spectroscopy. RESULTS: SB216763 treatment decreased choline incorporation into lipids and caused an accumulation of CDP-choline which was accompanied by decreased conversion of glucose into lipid components. CONCLUSION: SB216763 profoundly inhibits phospholipid synthesis in cancer cells which demonstrate accumulation of CDP-choline detectable by 31P NMR spectroscopy. Metabolic changes in lipid metabolism present potential response markers to drugs targeting GSK3.

Original publication

DOI

10.1007/s10334-018-0719-3

Type

Journal article

Journal

MAGMA

Publication Date

04/2019

Volume

32

Pages

227 - 235

Keywords

31P nuclear magnetic resonance spectroscopy, CDP-choline, Choline, Glucose, Glycogen synthase kinase 3, Lipid, Biomarkers, Tumor, Breast Neoplasms, Cell Line, Tumor, Choline, Colorectal Neoplasms, Cytidine Diphosphate Choline, Enzyme Inhibitors, Female, Glucose, Glycogen Synthase Kinase 3, Humans, Indoles, Lipid Metabolism, Magnetic Resonance Spectroscopy, Maleimides, Phosphatidylcholines