| First Author | Chen JX | Year | 2016 |
| Journal | Cancer Lett | Volume | 371 |
| Issue | 1 | Pages | 71-8 |
| PubMed ID | 26582657 | Mgi Jnum | J:237564 |
| Mgi Id | MGI:5816180 | Doi | 10.1016/j.canlet.2015.11.010 |
| Citation | Chen JX, et al. (2016) Dietary tocopherols inhibit PhIP-induced prostate carcinogenesis in CYP1A-humanized mice. Cancer Lett 371(1):71-8 |
| abstractText | Tocopherols, the major forms of vitamin E, exist as alpha-tocopherol (alpha-T), beta-T, gamma-T and delta-T. The cancer preventive activity of vitamin E is suggested by epidemiological studies, but recent large-scale cancer prevention trials with high dose of alpha-T yielded disappointing results. Our hypothesis that other forms of tocopherols have higher cancer preventive activities than alpha-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 gamma-T-rich mixture of tocopherols (gamma-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 delta-T, gamma-T or alpha-T (0.2% in diet) showed that delta-T was more effective than gamma-T or alpha-T in preventing mPIN formations and p-AKT elevation. These results indicate that gamma-TmT and delta-T could be effective preventive agents of prostate cancer. |
