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δ‐ and γ‐tocopherols inhibit phIP/DSS‐induced colon carcinogenesis by protection against early cellular and DNA damages
Author(s) -
Chen Jayson X.,
Liu Anna,
Lee MaoJung,
Wang Hong,
Yu Siyuan,
Chi Eric,
Reuhl Kenneth,
Suh Nanjoo,
Yang Chung S.
Publication year - 2017
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22481
Subject(s) - colorectal cancer , azoxymethane , carcinogen , nitrotyrosine , biology , oxidative stress , carcinogenesis , dna damage , cancer , colitis , pharmacology , vitamin e , cancer research , antioxidant , nitric oxide , immunology , biochemistry , endocrinology , nitric oxide synthase , dna , genetics
Tocopherols, the major forms of vitamin E, are a family of fat‐soluble compounds that exist in alpha (α‐T), beta (β‐T), gamma (γ‐T), and delta (δ‐T) variants. A cancer preventive effect of vitamin E is suggested by epidemiological studies. However, past animal studies and human intervention trials with α‐T, the most active vitamin E form, have yielded disappointing results. A possible explanation is that the cancer preventive activity of α‐T is weak compared to other tocopherol forms. In the present study, we investigated the effects of δ‐T, γ‐T, and α‐T (0.2% in diet) in a novel colon cancer model induced by the meat‐derived dietary carcinogen, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS)‐induced colitis in CYP1A‐humanized (hCYP1A) mice. PhIP/DSS treatments induced multiple polypoid tumors, mainly tubular adenocarcinomas, in the middle to distal colon of the hCYP1A mice after 10 wk. Dietary supplementation with δ‐T and γ‐T significantly reduced colon tumor formation and suppressed markers of oxidative and nitrosative stress (i.e., 8‐oxo‐dG and nitrotyrosine) as well as pro‐inflammatory mediators (i.e., NF‐κB p65 and p‐STAT3) in tumors and adjacent tissues. By administering δ‐T at different time periods, we obtained results suggesting that the inhibitory effect of δ‐T against colon carcinogenesis is mainly due to protection against early cellular and DNA damages caused by PhIP. α‐T was found to be ineffective in inhibiting colon tumors and less effective in attenuating the molecular changes. Altogether, we demonstrated strong cancer preventive effects of δ‐T and γ‐T in a physiologically relevant model of human colon cancer. © 2016 Wiley Periodicals, Inc.