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.
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 language | English |
|---|---|
| Pages (from-to) | 227-235 |
| Number of pages | 9 |
| Journal | Magnetic Resonance Materials in Physics, Biology and Medicine |
| Volume | 32 |
| Issue number | 2 |
| Early online date | 16 Nov 2018 |
| DOIs | |
| Publication status | Published - Apr 2019 |
Bibliographical note
Open via Springer Compact AgreementFunding from the University of Aberdeen Development Trust is gratefully acknowledged. Professor Zanda is gratefully acknowledged for the use of his NMR system.
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
Access to Document
- CDP-choline accumulation in breast and colorectal cancer cells treated with a GSK-3-targeting inhibitor
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.