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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Dietary tocopherols inhibit PhIP-induced prostate carcinogenesis in CYP1A-humanized mice.

Authors: Chen, Jayson X; Li, Guangxun; Wang, Hong; Liu, Anna; Lee, Mao-Jung; Reuhl, Kenneth; Suh, Nanjoo; Bosland, Maarten C; Yang, Chung S

Published In Cancer Lett, (2016 Feb 01)

Abstract: Tocopherols, the major forms of vitamin E, exist as alpha-tocopherol (α-T), β-T, γ-T and δ-T. The cancer preventive activity of vitamin E is suggested by epidemiological studies, but recent large-scale cancer prevention trials with high dose of α-T yielded disappointing results. Our hypothesis that other forms of tocopherols have higher cancer preventive activities than α-T was tested, herein, in a novel prostate carcinogenesis model induced by 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), a dietary carcinogen, in the CYP1A-humanized (hCYP1A) mice. Treatment of hCYP1A mice with PhIP (200 mg/kg b.w., i.g.) induced high percentages of mouse prostatic intraepithelial neoplasia (mPIN), mainly in the dorsolateral glands. Supplementation with a γ-T-rich mixture of tocopherols (γ-TmT, 0.3% in diet) significantly inhibited the development of mPIN lesions and reduced PhIP-induced elevation of 8-oxo-deoxyguanosine, COX-2, nitrotyrosine, Ki-67 and p-AKT, and the loss of PTEN and Nrf2. Further studies with purified δ-T, γ-T or α-T (0.2% in diet) showed that δ-T was more effective than γ-T or α-T in preventing mPIN formations and p-AKT elevation. These results indicate that γ-TmT and δ-T could be effective preventive agents of prostate cancer.

PubMed ID: 26582657 Exiting the NIEHS site

MeSH Terms: 8-Hydroxy-2'-Deoxyguanosine; Animals; Anticarcinogenic Agents/administration & dosage; Anticarcinogenic Agents/pharmacology*; Cyclooxygenase 2/metabolism; Cytochrome P-450 CYP1A2/genetics; Cytochrome P-450 CYP1A2/metabolism*; Deoxyguanosine/analogs & derivatives; Deoxyguanosine/metabolism; Diet*; Disease Models, Animal; Humans; Imidazoles*; Ki-67 Antigen/metabolism; Male; Mice, Transgenic; NF-E2-Related Factor 2/metabolism; PTEN Phosphohydrolase/metabolism; Phosphorylation; Prostatic Intraepithelial Neoplasia/chemically induced; Prostatic Intraepithelial Neoplasia/enzymology; Prostatic Intraepithelial Neoplasia/genetics; Prostatic Intraepithelial Neoplasia/pathology; Prostatic Intraepithelial Neoplasia/prevention & control*; Prostatic Neoplasms/chemically induced; Prostatic Neoplasms/enzymology; Prostatic Neoplasms/genetics; Prostatic Neoplasms/pathology; Prostatic Neoplasms/prevention & control*; Proto-Oncogene Proteins c-akt/metabolism; Signal Transduction/drug effects; Tocopherols/administration & dosage; Tocopherols/pharmacology*; Tyrosine/analogs & derivatives; Tyrosine/metabolism

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