title: Real-time changes in 1H and 31P NMR spectra of malignant human mammary epithelial cells during treatment with the anti-inflammatory agent indomethacin.
abstract: 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.
authors.affiliation: MR Oncology Section, Division of MR Research, Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Glunde
authors.forename: Ellen
authors.initials: E
authors.lastname: Ackerstaff
authors.forename: Kshama
authors.initials: K
authors.lastname: Natarajan
authors.forename: Dmitri
authors.initials: D
authors.lastname: Artemov
authors.forename: Zaver M
authors.initials: ZM
authors.lastname: Bhujwalla
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus / Q000737:chemistry; D014407:Tumor Cells, Cultured
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010710:Phosphates; D010758:Phosphorus; D002794:Choline; D007213:Indomethacin