Abstract
The antidiabetic drug metformin, currently undergoing trials for cancer treatment, modulates lipid and glucose metabolism both crucial in phospholipid synthesis. Here the effect of treatment of breast tumour cells with metformin on phosphatidylcholine (PtdCho) metabolism which plays a key role in membrane synthesis and intracellular signalling has been examined.
MethodsMDA-MB-468, BT474 and SKBr3 breast cancer cell lines were treated with metformin and [3H-methyl]choline and [14C(U)]glucose incorporation and lipid accumulation determined in the presence and absence of lipase inhibitors. Activities of choline kinase (CK), CTP:phosphocholine cytidylyl transferase (CCT) and PtdCho-phospholipase C (PLC) were also measured. [3H] Radiolabelled metabolites were determined using thin layer chromatography.
ResultsMetformin-treated cells exhibited decreased formation of [3H]phosphocholine but increased accumulation of [3H]choline by PtdCho. CK and PLC activities were decreased and CCT activity increased by metformin-treatment. [14C] incorporation into fatty acids was decreased and into glycerol was increased in breast cancer cells treated with metformin incubated with [14C(U)]glucose.
ConclusionThis is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.
| Original language | English |
|---|---|
| Article number | e0151179 |
| Pages (from-to) | 1-17 |
| Number of pages | 17 |
| Journal | PloS ONE |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 9 Mar 2016 |
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- Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells
Copyright: © 2016 Smith, Phyu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/4.0/