Abstract 1520: Simvastatin alters oxysterol profiles in TRAMP mice.

Due to mounting epidemiological data evidence, we sought to determine if simvastatin, the most widely used cholesterol lowering medication, could alter prostate cancer incidence in the TRAMP mouse model of prostate cancer. We hypothesized that simvastatin would inhibit advanced prostate cancer formation. Two separate studies were performed using high doses of simvastatin (up to 0.050% w/w) or simvastatin plus genistein in a high fat Western diet. While prostate cancer incidence was only moderately reduced, surprising changes in the serum oxysterol profiles of the TRAMP mice were detected. Oxysterols, oxygenated derivatives of cholesterol, have recently been shown to influence human diseases, and here we suggest that five oxysterols may play a role in prostate cancer progression. Ten mice were chosen from each treatment group, and their serum oxysterol profiles were analyzed by LC-MS-MS. The oxysterol that was most responsive to treatment was 24(S)-hydroxycholesterol, reducing significantly in all treatment groups. 24(S)-OHC was reduced from the control at 20 ng/mL to 10 ng/mL with statin treatment (p-value Citation Format: Sara K. Drenkhahn, Glenn A. Jackson, Nicholas J.E. Starkey, Yufei Li, Roxanne E. Gelven, Charles E. Wiedmeyer, Jim D. Browning, Kevin L. Fritsche, Cynthia L. Besch-Williford, Dennis B. Lubahn. Simvastatin alters oxysterol profiles in TRAMP mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1520. doi:10.1158/1538-7445.AM2013-1520