Real-time changes in 1H and 31P NMR spectra of malignant human mammary epithelial cells during treatment with the anti-inflammatory agent indomethacin

Magn Reson Med. 2002 Nov;48(5):819-25. doi: 10.1002/mrm.10295.


Choline metabolites in malignant human mammary epithelial cells (HMECs) are significantly altered compared to normal HMECs. (1)H NMR studies of cell extracts have shown that treatment of malignant HMECs with a nonsteroidal anti-inflammatory agent, indomethacin, results in a distribution of choline compounds more typical of nonmalignant HMECs. To follow the time course of these changes, in this study real-time monitoring of choline compounds of malignant MDA-MB-231 cells was performed during treatment with indomethacin. The contribution of changes in intra- and extracellular pH to changes in choline compounds was also examined. Changes in water-soluble choline phospholipid metabolites, such as phosphocholine (PC), glycerophosphocholine (GPC), and total choline, as well as intracellular pH, were monitored by (31)P and diffusion-weighted (1)H NMR spectroscopy of living cells using an NMR-compatible perfusion system. An accumulation of GPC and a decrease of PC, resulting in an increased [GPC]/[PC] ratio, were detected within 2 hr of treatment with 200 microM indomethacin. Since a decreased [GPC]/[PC] ratio is associated with increased malignancy, these data demonstrate that nonspecific cyclooxygenase inhibition by indomethacin alters the choline metabolite profile of malignant cells towards a less malignant phenotype. These changes were not related to alterations of intra- or extracellular pH.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Breast Neoplasms / metabolism*
  • Choline / metabolism
  • Epithelial Cells / metabolism*
  • Female
  • Humans
  • Hydrogen-Ion Concentration
  • Indomethacin / pharmacology*
  • Magnetic Resonance Spectroscopy*
  • Phosphates / metabolism
  • Phosphorus / chemistry
  • Tumor Cells, Cultured


  • Anti-Inflammatory Agents, Non-Steroidal
  • Phosphates
  • Phosphorus
  • Choline
  • Indomethacin