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High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice
Author(s) -
Chang SeoNa,
Han Juhee,
Abdelkader Tamer Said,
Kim TaeHyoun,
Lee Ji Min,
Song Juha,
Kim KyungSul,
Park JongHwan,
Park JaeHak
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22843
Subject(s) - tramp , prostate cancer , endocrinology , medicine , prostate , glutathione peroxidase , gpx1 , gpx3 , gpx4 , oxidative stress , cancer , catalase
BACKGROUND Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high‐fat Western‐style diet is a known risk factor for prostate cancer and increases oxidative stress. METHODS We evaluated the association between dietary animal fat and expression of antioxidant enzymes, particularly glutathione peroxidase 3 (GPx3), in the early stages of transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Six‐week‐old male nontransgenic and TRAMP mice were placed on high animal fat (45% Kcal fat) or control (10% Kcal fat) diets and sacrificed after 5 or 10 weeks. RESULTS The histopathological score increased with age and high‐fat diet consumption. The histopathological scores in dorsal and lateral lobes increased in the 10‐week high‐fat diet group (6.2 ± 0.2 and 6.2 ± 0.4, respectively) versus the 10‐week control diet group (5.3 ± 0.3 and 5.2 ± 0.2, respectively). GPx3 decreased both at the mRNA and protein levels in mouse prostate. GPx3 mRNA expression decreased (∼36.27% and ∼23.91%, respectively) in the anterior and dorsolateral prostate of TRAMP mice fed a high‐fat diet compared to TRAMP mice fed a control diet. Cholesterol treatment increased PC‐3 human prostate cancer cell proliferation, decreased GPx3 mRNA and protein levels, and increased H 2 O 2 levels in culture medium. Moreover, increasing GPx3 mRNA expression by troglitazone in PC‐3 cells decreased cell proliferation and lowered H 2 O 2 levels. CONCLUSIONS Dietary fat enhances prostate cancer progression, possibly by suppressing GPx3 expression and increasing proliferation of prostate intraepithelial neoplasia (PIN) epithelial cells. Prostate 74: 1266–1277, 2014 . © 2014 Wiley Periodicals, Inc.