CDP-choline Accumulation in Breast and Colorectal Cancer Cells Treated with a GSK-3-targeting Inhibitor

Overview

Journal MAGMA

Publisher Springer

Date 2018 Nov 18

PMID 30446846

Citations 2

Authors

Su Myat Phyu

Chih-Chung Tseng

Tim Andrew Davies Smith

Affiliations

Soon will be listed here.

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

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