Potential metabolomic biomarkers for evaluation of adriamycin efficacy using a urinary 1H-NMR spectroscopy
Article first published online: 11 JUL 2012
Copyright © 2012 John Wiley & Sons, Ltd.
Journal of Applied Toxicology
Volume 33, Issue 11, pages 1251–1259, November 2013
How to Cite
Kim, K.-B., Yang, J.-Y., Kwack, S. J., Kim, H. S., Ryu, D. H., Kim, Y.-J., Bae, J. Y., Lim, D. S., Choi, S. M., Kwon, M. J., Bang, D. Y., Lim, S. K., Kim, Y. W., Hwang, G.-S. and Lee, B.-M. (2013), Potential metabolomic biomarkers for evaluation of adriamycin efficacy using a urinary 1H-NMR spectroscopy. J. Appl. Toxicol., 33: 1251–1259. doi: 10.1002/jat.2778
- Issue published online: 20 SEP 2013
- Article first published online: 11 JUL 2012
- Manuscript Revised: 19 APR 2012
- Manuscript Accepted: 19 APR 2012
- Manuscript Received: 2 FEB 2012
- gastric cancer;
- 1H NMR
A metabolomics approach using proton nuclear magnetic resonance (NMR) was applied to investigate metabolic alterations following adriamycin (ADR) treatment for gastric adenocarcinoma. After BALB/c-nu/nu mice were implanted with human gastric adenocarcinoma, ADR (1 or 3 mg kg−1 per day) was intraperitoneally administered for 5 days. Urine was collected on days 2 and 5 and analyzed by NMR. The levels of trimethylamine oxide (TMAO, ×0.3), hippurate (×0.3) and taurine (×0.6) decreased significantly (P < 0.05), whereas the levels of 3-indoxylsulfate (×12.6), trigonelline (×1.5), citrate (×2.5), trimethylamine (TMA, ×2.0) and 2-oxoglutarate (×2.3) increased significantly (P < 0.05) in the tumor model. After ADR treatment, TMAO, hippuarte and taurine were increased significantly on day 5 compared with those of the tumor model. The levels of 2-oxoglutarate, 3-indoxylsulfate, trigonelline, TMA and citrate, which increased in the tumor model, significantly decreased to those of normal control by ADR treatment. Furthermore, the ratio between TMA and TMAO was dramatically altered in both tumor and ADR-treated groups. Overall, metabolites such as TMAO, TMA, 3-indoxylsulfate, hippurate, trigonelline, citrate and 2-oxoglutarate related to the tricarboxylic acid (TCA) cycle might be considered as therapeutic targets to potentiate the efficacy of ADR. Thus, these results suggest that the metabolomics analysis of tumor response to ADR treatment may be applicable for demonstrating the efficacy of anticancer agent, ADR and treatment adaptation. Copyright © 2012 John Wiley & Sons, Ltd.