title: Modulation of choline kinase activity in human cancer cells observed by dynamic 31P NMR.
abstract: Choline metabolites are widely studied in cancer research as biomarkers of malignancy and as indicators of therapeutic response. However, endogenous phosphocholine levels are determined by a number of processes that confound the interpretation of these measurements, including membrane transport rates and a series of enzyme catalysed reactions in the Kennedy pathway. Employing a dynamic (31)P NMR assay that is specific to choline kinase (ChoK) we have measured the rates of this enzyme reaction in cell lysates of MDA-MB-231 breast, PC-3 prostate and HeLa cervical cancer cells and in solutions of purified human ChoK. The rates are sensitive to inhibition by hemicholinium-3 (HC-3), a competitive ChoK inhibitor, and to N-[2-bromocinnamyl(amino)ethyl]-5-isoquinolinesulphonamide (H-89), an agent commercialized as a specific cyclic-AMP-dependent protein kinase A (PKA) inhibitor.
authors.affiliation: Cancer Research UK Clinical Magnetic Resonance Research Group, The Institute of Cancer Research, Royal Marsden NHS Foundation Trust, Downs Road, Sutton, Surrey, SM2 5PT, UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gabellieri
authors.forename: Mounia
authors.initials: M
authors.lastname: Beloueche-Babari
authors.forename: Yann
authors.initials: Y
authors.lastname: Jamin
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Payne
authors.forename: Martin O
authors.initials: MO
authors.lastname: Leach
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Eykyn
mesh_terms: D045744:Cell Line, Tumor; D002797:Choline Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D010759:Phosphorus Isotopes; D010766:Phosphorylation / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D007546:Isoquinolines; D010759:Phosphorus Isotopes; D013449:Sulfonamides; D002797:Choline Kinase; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide