A gamma-tocopherol-rich mixture of tocopherols inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sulfate sodium-treated mice.
We investigated the effects of a gamma-tocopherol-rich mixture of tocopherols (gamma-TmT, containing 57% gamma-T, 24% delta-T, and 13% alpha-T) on colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. In experiment 1, 6-week-old male CF-1 mice were given a dose of AOM (10 mg/kg body weight, i.p.), and 1 week later, 1.5% DSS in drinking water for 1 week. The mice were maintained on either a gamma-TmT (0.3%)-enriched or a standard AIN93M diet, starting 1 week before the AOM injection, until the termination of experiment. In the AOM/DSS-treated mice, dietary gamma-TmT treatment resulted in a significantly lower colon inflammation index (52% of the control) on day 7 and number of colon adenomas (9% of the control) on week 7. gamma-TmT treatment also resulted in higher apoptotic index in adenomas, lower prostaglandin E2, leukotriene B4, and nitrotyrosine levels in the colon, and lower prostaglandin E2, leukotriene B4, and 8-isoprostane levels in the plasma on week 7. Some of the decreases were observed even on day 7. In experiment 2 with AOM/DSS- treated mice sacrificed on week 21, dietary 0.17% or 0.3% gamma-TmT treatment, starting 1 week before the AOM injection, significantly inhibited adenocarcinoma and adenoma formation in the colon (to 17-33% of the control). Dietary 0.3% gamma-TmT that was initiated after DSS treatment also exhibited a similar inhibitory activity. The present study showed that gamma-TmT effectively inhibited colon carcinogenesis in AOM/DSS-treated mice, and the inhibition may be due to the apoptosis-inducing, anti-inflammatory, antioxidative, and reactive nitrogen species-trapping activities of tocopherols.
Ju
Jihyeung
J
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, and Center for Cancer Prevention Research, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA.
Hao
Xingpei
X
Lee
Mao-Jung
MJ
Lambert
Joshua D
JD
Lu
Gang
G
Xiao
Hang
H
Newmark
Harold L
HL
Yang
Chung S
CS
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D003043:Cocarcinogenesis; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D016264:Dextran Sulfate / Q000633:toxicity*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D015232:Dinoprostone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000188:drug therapy*; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D051379:Mice; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood; D024504:gamma-Tocopherol / Q000627:therapeutic use*
D000975:Antioxidants; D002273:Carcinogens; D007975:Leukotriene B4; C075750:8-epi-prostaglandin F2alpha; C002744:3-nitrotyrosine; D014443:Tyrosine; D024504:gamma-Tocopherol; D016264:Dextran Sulfate; D015237:Dinoprost; D015232:Dinoprostone; D001397:Azoxymethane