Cellular environment of metabolites and a metabonomic study of tamoxifen in endometrial cells using gradient high resolution magic angle spinning 1H NMR spectroscopy

High resolution magic angle spinning (HRMAS) (HNMR)-H-1 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 muM 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-mositol resonances (3.30, 3.62, 3.55 ppm). The nucleotide changes suggest that tamoxifen affects RNA transcription, while the changes in ethanolamine and myo-mositol concentrations are indicative of cell membrane turnover. (C) 2002 Elsevier Science B.V All rights reserved.