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- Title
CDP-choline accumulation in breast and colorectal cancer cells treated with a GSK-3-targeting inhibitor.
- Authors
Phyu, Su Myat; Tseng, Chih-Chung; Smith, Tim Andrew Davies
- Abstract
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.
- Subjects
GLYCOGEN synthase kinase-3; GLYCOGEN synthase kinase; CANCER cells; COLORECTAL cancer; BREAST cancer; LIPID metabolism
- Publication
MAGMA: Magnetic Resonance Materials in Physics, Biology & Medicine, 2019, Vol 32, Issue 2, p227
- ISSN
0968-5243
- Publication type
Article
- DOI
10.1007/s10334-018-0719-3