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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Gamma-tocopherol-enriched mixed tocopherol diet inhibits prostate carcinogenesis in TRAMP mice.

Authors: Barve, Avantika; Khor, Tin Oo; Nair, Sujit; Reuhl, Kenneth; Suh, Nanjoo; Reddy, Bandaru; Newmark, Harold; Kong, Ah-Ng

Published In Int J Cancer, (2009 Apr 01)

Abstract: Gamma-tocopherol (gamma-T) alone or in combination with alpha-tocopherol has been shown to suppress biomarkers of oxidative stress in asthamatics and human subjects with metabolic syndrome. Oxidative stress has been implicated as a key event in prostate carcinogenesis. Hence, the purpose of this study was to examine the effects of gamma-tocopherol-enriched mixed tocopherol diet on prostate carcinogenesis in a murine prostate cancer model (TRAMP). 8 week old TRAMP males were fed 0.1% gamma-T-enriched mixed tocopherol diet that contained 20-fold higher levels of gamma-tocopherol, and roughly 3-fold higher levels of alpha-tocopherol. The effect of such diet on tumor and PIN development was observed. The expression of phase II detoxifying, antioxidant enzymes and Nrf2 mRNA and protein were determined by RT-PCR, immunohistochemistry and western blotting techniques. Treatment with gamma-T-enriched mixed tocopherols significantly suppressed the incidence of palpable tumor and Prostate Intraepithelial Neoplasia (PIN) development without affecting the expression of the transgene (SV-40). Tumor progression occurred with a significant suppression of antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase, heme-oxygenase-1 and phase II detoxifying enzymes. Treatment with gamma-T-enriched mixed tocopherol diet upregulated the expression of most detoxifying and antioxidant enzymes. Nrf2-a redox sensitive transcription factor known to mediate the expression of phase II detoxifying enzymes, was also significantly upregulated following treatment with gamma-T-enriched mixed tocopherol diet. Gamma-T-enriched mixed tocopherols significantly up-regulated the expression of Nrf2 and its related detoxifying and antioxidant enzymes thereby suppressing PIN and tumor development.

PubMed ID: 19115203 Exiting the NIEHS site

MeSH Terms: Animals; Antioxidants/metabolism; Antioxidants/pharmacology*; Blotting, Western; Diet; Disease Models, Animal; Immunohistochemistry; Male; Metabolic Detoxication, Phase II; Mice; NF-E2-Related Factor 2/metabolism; Oxidoreductases/metabolism; Prostatic Neoplasms/diet therapy*; Prostatic Neoplasms/prevention & control*; RNA/analysis; Reverse Transcriptase Polymerase Chain Reaction; Tocopherols/therapeutic use*; gamma-Tocopherol/therapeutic use*

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