CDP-choline accumulation in breast and colorectal cancer cells treated with a GSK-3-targeting inhibitor

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 [(14)C (U)] glucose and [(3)H] choline incorporation into lipids was determined. Cell extracts from treated cells were subject to (31)P 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 (31)P NMR spectroscopy. Metabolic changes in lipid metabolism present potential response markers to drugs targeting GSK3.