title: Cellular environment of metabolites and a metabonomic study of tamoxifen in endometrial cells using gradient high resolution magic angle spinning 1H NMR spectroscopy.
abstract: High resolution magic angle spinning (HRMAS) 1H NMR spectroscopy was used to metabolically characterise Ishikawa cells, a human cell line derived from endometrial adenocarcinoma. The spectra obtained had well-resolved resonances from the nucleotide derivatives of uridine and adenosine. Using a combination of diffusion- and relaxation-weighted spectroscopy, the cellular environment of key metabolites previously identified as related to cell growth was also investigated. As Ishikawa cells are hormone-responsive, the metabolic action of tamoxifen, a selective estrogen receptor modulator (SERM), was also investigated. Cells were exposed to 5, 1 and 0.1 microM tamoxifen. Using the statistical regression technique of prediction to latent structures by partial least squares, a predictive model was built modelling the metabolic profile of the cells against exposure to tamoxifen. These spectral changes were characterised by increased resonance intensities from ethanolamine (3.26 ppm), glucose (3.34-3.94 ppm), glutamate (2.14, 2.32 ppm), tyrosine (7.24 ppm), uridine (7.85 ppm) and adenosine (8.20 ppm), and a relative decrease in contributions from myo-inositol resonances (3.30, 3.62, 3.55 ppm). The nucleotide changes suggest that tamoxifen affects RNA transcription, while the changes in ethanolamine and myo-inositol concentrations are indicative of cell membrane turnover.
authors.affiliation: Biological Chemistry, Biomedical Sciences, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Exhibition Road, South Kensington, London SW7 2AZ, UK. j.griffin@ic.ac.uk
authors.forename: J L
authors.initials: JL
authors.lastname: Griffin
authors.forename: J C M
authors.initials: JC
authors.lastname: Pole
authors.forename: J K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: P L
authors.initials: PL
authors.lastname: Carmichael
mesh_terms: D000230:Adenocarcinoma; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016889:Endometrial Neoplasms; D004717:Endometrium / Q000378:metabolism*; D020847:Estrogen Receptor Modulators / Q000378:metabolism*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011237:Predictive Value of Tests; D013629:Tamoxifen / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D020847:Estrogen Receptor Modulators; D013629:Tamoxifen