Citrus nobiletin inhibits azoxymethane-induced large bowel carcinogenesis in rats.
The inhibitory effects of dietary feeding of citrus nobiletin on azoxymethane (AOM)-induced rat colon carcinogenesis using a long-term bioassay were investigated. Five-week old male F344 rats were initiated with two weekly subcutaneous injections of AOM (20 mg/kg bw) to induce colonic tumors. They were also given the diets containing 0.01% or 0.05% nobiletin for 34 weeks, starting one week after the last dosing of AOM. At the end of the study, the incidence of colonic adenocarcinoma were 67% in the AOM alone group, 55% in the AOM-->0.01% nobiletin group, 35% (p<0.05) in the AOM-->0.05% nobiletin group. Also, nobiletin feeding reduced the cell-proliferation activity, increased the apoptotic index, and decreased the prostaglandin E2 content in colonic adenocarcinoma and/or colonic mucosa. These findings might suggest that citrus nobiletin has chemopreventive ability against AOM-induced rat colon carcinogenesis.
Suzuki
Rikako
R
The First Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. rikako@kanazawa-med.ac.jp
Kohno
Hiroyuki
H
Murakami
Akira
A
Koshimizu
Koichi
K
Ohigashi
Hajime
H
Yano
Masamichi
M
Tokuda
Harukuni
H
Nishino
Hoyoku
H
Tanaka
Takuji
T
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane; D002957:Citrus; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D015232:Dinoprostone / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008517:Phytotherapy; D011073:Polyamines / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344
D016588:Anticarcinogenic Agents; D047309:Flavones; D011073:Polyamines; D018809:Proliferating Cell Nuclear Antigen; C008661:nobiletin; D015232:Dinoprostone; D001397:Azoxymethane