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

Su Myat Phyu, Chih-Chung Tseng, Tim Andrew Davies Smith (Corresponding Author)

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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.
Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalMagnetic Resonance Materials in Physics, Biology and Medicine
Volume32
Issue number2
Early online date16 Nov 2018
DOIs
Publication statusPublished - Apr 2019

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Keywords

  • glycogen synthase kinase 3 (GSK3)
  • CDP-choline
  • 31P nuclear magnetic resonance spectroscopy
  • lipid
  • glucose
  • choline
  • Choline
  • Glycogen synthase kinase 3
  • 31 P nuclear magnetic resonance spectroscopy
  • Glucose
  • Lipid
  • APOPTOSIS
  • GLYCOGEN-SYNTHASE KINASE-3
  • TRANSPORT
  • METABOLISM
  • PATHWAY
  • PHOSPHATIDYLCHOLINE
  • P-31 nuclear magnetic resonance spectroscopy

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