title: Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  MDA-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.
  
  
  RESULTS
  Metformin-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.
  
  
  CONCLUSIONS
  This is the first study to show that treatment of breast cancer cells with metformin induces profound changes in phospholipid metabolism.
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
authors.forename: Tim A D
authors.initials: TA
authors.lastname: Smith
authors.affiliation: School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen, United Kingdom.
authors.forename: Su M
authors.initials: SM
authors.lastname: Phyu
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002794:Choline / Q000378:metabolism; D005260:Female; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism*
chemical_list: D010713:Phosphatidylcholines; D010743:Phospholipids; D008687:Metformin; D002794:Choline