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Silibinin Feeding Alters the Metabolic Profile in TRAMP Prostatic Tumors: ¹H-NMRS–Based Metabolomics Study

Departments of ¹ Pharmaceutical Sciences and ² Anesthesiology and Radiology, and ³ University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado

Requests for reprints: Rajesh Agarwal, University of Colorado Denver, C238-P15, Research 2, 12700 East 19th Avenue, Room 3121, Aurora, CO 80045. Phone: 303-724-4055; Fax: 303-724-7266; E-mail: Rajesh.Agarwal{at}UCDenver.edu.

Key Words: chemoprevention • metabolomics • prostate cancer

Herein, we evaluated for the first time silibinin efficacy on prostate cancer (PCa) metabolism in transgenic adenocarcinoma of the mouse prostate (TRAMP) model using quantitative high-resolution proton nuclear magnetic resonance spectroscopy metabolomics. Prostate tissues were from mice fed control or silibinin diet for 20 weeks. Comparative metabolic profiling indicated that antitumor effect of silibinin is accompanied by alteration in metabolic profile of TRAMP prostatic tumors as indicated by 6-fold (P = 0.016) increase in glucose content and 48% (P = 0.015) reduction in lactate levels. Increase in citrate use by prostate tissue also reversed with silibinin, as indicated by 3-fold (P = 0.01) increase in citrate levels in silibinin-fed group. Also, 61% and 50% (P < 0.01) decrease in cholesterol and phosphatidylcholine levels, respectively, was observed with silibinin. These results corroborate our earlier findings regarding PCa chemopreventive potential of silibinin in TRAMP model and warrant additional metabolic profiling in other silibinin-fed PCa tumor model tissues. This will help identify specific metabolic biomarkers altered during silibinin treatment, which when detected in clinical biopsies or noninvasive magnetic resonance spectroscopic studies could help monitor silibinin effectiveness against PCa malignancy. [Cancer Res 2009;69(9):3731–5]