Dietary tricin suppresses inflammation-related colon carcinogenesis in male Crj: CD-1 mice.
The flavone 4',5,7-trihydroxy-3',5'-dimethoxyflavone (tricin) present in rice, oats, barley, and wheat exhibits antigrowth activity in several human cancer cell lines and anti-inflammatory potential. However, the chemopreventive activity has not yet been elucidated in preclinical animal models of colorectal cancer. This study was designed to determine whether dietary tricin exerts inflammation-associated colon carcinogenesis induced by azoxymethane and dextran sulfate sodium in mice. Male Crj: CD-1 mice were initiated with a single i.p. injection of azoxymethane (10 mg/kg body weight) and followed by a 1-week exposure to dextran sulfate sodium (1.5%, w/v) in drinking water to induce colonic neoplasms. They were then given the experimental diet containing 50 or 250 ppm tricin. The experiment was terminated at week 18 to determine the chemopreventive efficacy of tricin. In addition, the effects of dietary tricin on the expression of several inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, were assayed. The development of colonic adenomas and adenocarcinomas was significantly reduced by feeding with 50 and 250 ppm tricin, respectively. Dietary tricin also significantly reduced the proliferation of adenocarcinoma cells as well as the numbers of mitoses/anaphase bridging in adenocarcinoma cells. The dietary administration with tricin significantly inhibited the expression of TNF-alpha in the nonlesional cypts. Our findings that dietary tricin inhibits inflammation-related mouse colon carcinogenesis by suppressing the expression of TNF-alpha in the nonlesional cyrpts and the proliferation of adenocarcinomas suggest a potential use of tricin for clinical trials of colorectal cancer chemoprevention.
Oyama
Takeru
T
Department of Oncologic Pathology, Kanazawa Medical University, Ishikawa 920-0293, Japan.
Yasui
Yumiko
Y
Sugie
Shigeyuki
S
Koketsu
Mamoru
M
Watanabe
Kunitomo
K
Tanaka
Takuji
T
D000230:Adenocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000236:Adenoma / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D004032:Diet; D005419:Flavonoids / Q000008:administration & dosage*; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002273:Carcinogens; D005419:Flavonoids; D010936:Plant Extracts; D012333:RNA, Messenger; C017769:tricin; D001397:Azoxymethane