27 Citations (Scopus)

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

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Prostatic Intraepithelial Neoplasia
Methionine
Transgenic Mice
Prostate
Adenocarcinoma
Prostatic Neoplasms
Diet
Laboratory Animals
Cerebral Palsy
Insulin-Like Growth Factor I
Carcinogenesis
Chronic Disease

All Science Journal Classification (ASJC) codes

  • Oncology
  • Urology

Cite this

Sinha, Raghu ; Cooper, Timothy ; Rogers, Connie Jo ; Sinha, Indu ; Turbitt, William J. ; Calcagnotto, Ana ; Perrone, Carmen E. ; Richie, John. / Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice. In: Prostate. 2014 ; Vol. 74, No. 16. pp. 1663-1673.
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title = "Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice",
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.",
author = "Raghu Sinha and Timothy Cooper and Rogers, {Connie Jo} and Indu Sinha and Turbitt, {William J.} and Ana Calcagnotto and Perrone, {Carmen E.} and John Richie",
year = "2014",
month = "1",
day = "1",
doi = "10.1002/pros.22884",
language = "English (US)",
volume = "74",
pages = "1663--1673",
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Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice. / Sinha, Raghu; Cooper, Timothy; Rogers, Connie Jo; Sinha, Indu; Turbitt, William J.; Calcagnotto, Ana; Perrone, Carmen E.; Richie, John.

In: Prostate, Vol. 74, No. 16, 01.01.2014, p. 1663-1673.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Dietary methionine restriction inhibits prostatic intraepithelial neoplasia in TRAMP mice

AU - Sinha, Raghu

AU - Cooper, Timothy

AU - Rogers, Connie Jo

AU - Sinha, Indu

AU - Turbitt, William J.

AU - Calcagnotto, Ana

AU - Perrone, Carmen E.

AU - Richie, John

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

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U2 - 10.1002/pros.22884

DO - 10.1002/pros.22884

M3 - Article

C2 - 25250521

AN - SCOPUS:84921977238

VL - 74

SP - 1663

EP - 1673

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 16

ER -