Regular exercise reduces colon tumorigenesis associated with suppression of iNOS.
Several epidemiological studies have shown that regular exercise can prevent the onset of colon cancer, although the mechanism involved is unclear. Expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) is often elevated in an initial step of tumorigenesis and promotes colorectal cancer. We investigated the effect of exercise on colon tumorigenesis associated with iNOS and COX-2 in azoxymethan (AOM)-injected mice. Balb/c mice (8 weeks old) were divided into three groups of 20 animals each, consisting of a sedentary control group, an AOM group, and an exercise plus AOM group. Mice in the groups receiving AOM were injected intraperitoneally with AOM weekly for 2 weeks. Six weeks of regular exercise suppressed the generation of aberrant crypt foci (ACF) in the colon by AOM. Expression of iNOS was decreased by exercise compared with that in sedentary mice along with lower nitrotyrosine level while COX-2 was not changed by either AOM or exercise. Additionally, tumor necrosis factor alpha (TNFalpha) was decreased by exercise in the colon and plasma. There was no effect of exercise on the expression of antioxidant enzymes and chaperon protein in the colon. Our results suggest that regular exercise prevents colon tumorigenesis, at least partly via the suppression of iNOS expression associated with anti-inflammation.
Aoi
Wataru
W
Kyoto Prefectural University, Japan. waoi@koto.kpu-m.ac.jp
Naito
Yuji
Y
Takagi
Tomohisa
T
Kokura
Satoshi
S
Mizushima
Katsura
K
Takanami
Yoshikazu
Y
Kawai
Yukari
Y
Tanimura
Yuko
Y
Hung
Liu Po
LP
Koyama
Ryota
R
Ichikawa
Hiroshi
H
Yoshikawa
Toshikazu
T
D000818:Animals; D001397:Azoxymethane / Q000633:toxicity; D001835:Body Weight; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D010805:Physical Conditioning, Animal; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D002950:Citrate (si)-Synthase; D001397:Azoxymethane