title: δ- and γ-tocopherols inhibit phIP/DSS-induced colon carcinogenesis by protection against early cellular and DNA damages.
abstract: 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.
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Jayson X
authors.initials: JX
authors.lastname: Chen
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Anna
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Mao-Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.
authors.forename: Eric
authors.initials: E
authors.lastname: Chi
authors.affiliation: Department of Pharmacology and Toxicology, Rutgers, The State University of New Jersey, Piscataway, New Jersey.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Reuhl
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.|Cancer Institute of New Jersey, New Brunswick, New Jersey.
authors.forename: Nanjoo
authors.initials: N
authors.lastname: Suh
authors.affiliation: Department of Chemical Biology and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Piscataway, New Jersey.|Cancer Institute of New Jersey, New Brunswick, New Jersey.
authors.forename: Chung S
authors.initials: CS
authors.lastname: Yang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D016264:Dextran Sulfate; D006801:Humans; D007093:Imidazoles; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D024505:Tocopherols / Q000627:therapeutic use*; D014815:Vitamins / Q000627:therapeutic use*; D024504:gamma-Tocopherol / Q000627:therapeutic use*
chemical_list: D016588:Anticarcinogenic Agents; D007093:Imidazoles; D014815:Vitamins; D024504:gamma-Tocopherol; D016264:Dextran Sulfate; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D019363:Cytochrome P-450 CYP1A1; C479072:delta-tocopherol; D024505:Tocopherols
keywords: DSS; PhIP; chemoprevention; colon carcinogenesis; tocopherols