Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice

Raghu Sinha, Timothy Cooper, Connie Jo Rogers, Indu Sinha, William J. Turbitt, Ana Calcagnotto, Carmen E. Perrone, John Richie

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

Abstract

BACKGROUND Prostate cancer (PCa) is a major aging-related disease for which little progress has been made in developing preventive strategies. Over the past several years, methionine restriction (MR), the feeding of a diet low in methionine (Met), has been identified as an intervention which significantly extends lifespan and reduces the onset of chronic diseases, including cancer, in laboratory animals. We, therefore, hypothesized that MR may be an effective strategy for inhibiting PCa. METHODS Control (0.86% Met) or MR (0.12% Met) diets were fed to 5-week old TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice, a well-characterized model for PCa. The mice were sacrificed at 16 weeks of age and prostate and other tissues were harvested for histological and biochemical analyses. RESULTS As previously reported, MR was associated with a decrease in body weight which was not associated with lowered food intake. MR led to significant reductions in the development of Prostatic Intraepithelial Neoplasia (PIN) lesions, specifically in the anterior and dorsal lobes of the prostate where the incidence of high-grade PIN was reduced by ∼50% (P < 0.02). The reduction in PIN severity was associated with 46-64% reductions in cell proliferation rates (P < 0.02) and plasma IGF-1 levels (P < 0.0001), which might, in part, explain the effects on carcinogenesis. Additionally, no adverse consequences of MR on immune function were observed in the TRAMP mice. CONCLUSIONS Overall, these findings indicate that MR is associated with a reduction in prostate cancer development in the TRAMP model and supports the continued development of MR as a potential PCa prevention strategy.

Original languageEnglish (US)
Pages (from-to)1663-1673
Number of pages11
JournalProstate
Volume74
Issue number16
DOIs
StatePublished - Jan 1 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Fingerprint Dive into the research topics of 'Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice'. Together they form a unique fingerprint.

Cite this