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Cancer Lett. 2016 Feb 1;371(1):71-8. doi: 10.1016/j.canlet.2015.11.010. Epub 2015 Nov 12.

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

Author information

1
Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ, USA; Joint Graduate Program in Toxicology, Piscataway, NJ, USA.
2
Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ, USA.
3
Department of Pharmacology and Toxicology, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
4
Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ, USA; Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA.
5
Department of Pathology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
6
Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, NJ, USA; Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA. Electronic address: csyang@pharmacy.rutgers.edu.

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.

KEYWORDS:

PhIP; Prostate carcinogenesis; Tocopherols; mPIN; p-AKT

PMID:
26582657
PMCID:
PMC4721244
DOI:
10.1016/j.canlet.2015.11.010
[Indexed for MEDLINE]
Free PMC Article

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