Modulation of choline kinase activity in human cancer cells observed by dynamic 31P NMR

NMR Biomed. 2009 May;22(4):456-61. doi: 10.1002/nbm.1361.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Choline Kinase / antagonists & inhibitors
  • Choline Kinase / metabolism*
  • Humans
  • Isoquinolines / pharmacology
  • Magnetic Resonance Spectroscopy
  • Neoplasms / enzymology*
  • Neoplasms / pathology
  • Phosphorus Isotopes
  • Phosphorylation / drug effects
  • Sulfonamides / pharmacology
  • Time Factors

Substances

  • Isoquinolines
  • Phosphorus Isotopes
  • Sulfonamides
  • Choline Kinase
  • N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide