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- Title
Protection from inflammatory bowel disease and colitis-associated carcinogenesis with 4-vinyl-2,6-dimethoxyphenol (canolol) involves suppression of oxidative stress and inflammatory cytokines.
- Authors
Fang, Jun; Seki, Takahiro; Tsukamoto, Tetsuya; Qin, Haibo; Yin, Hongzhuan; Liao, Long; Nakamura, Hideaki; Maeda, Hiroshi
- Abstract
Oxidative stress is associated with various pathological processes including inflammatory bowel disease, which is a major cause of colon cancer. Here, we examined the antioxidative and anti-inflammatory effects of 4-vinyl-2,6-dimethoxyphenol (canolol), a potent antioxidant compound obtained from crude canola oil. Oral administration of 2% dextran sulfate sodium (DSS) resulted in the progression of colitis with shortening of the large bowel length. Administering a diet containing canolol significantly suppressed pathogenesis; diarrhea markedly improved and the length of large bowel returned to almost normal. Pathological examination clearly revealed improvement of colonic ulcers. Production of inflammatory cytokines, i.e. interleukin-12 and tumor necrosis factor-α, was significantly increased during this pathological process; their production was markedly inhibited by canolol. In the azoxymethane/DSS-induced colon cancer model, mice receiving canolol had a reduced occurrence of cancer, to 60%, compared with control mice, 100% of which had colon cancer. The numbers of tumors in each mouse were also significantly reduced in mice receiving the canolol-containing diet (5.6±2.0) compared with azoxymethane/DSS control mice (10.8±4.2). No apparent toxicity of canolol was observed. Moreover, inflammatory cytokines (i.e. cyclooxygenase-2, inducible nitric oxide synthase and tumor necrosis factor-α) and oxidative responding molecules, i.e. heme oxygenase-1, in colon were suppressed during this treatment. In a mouse colon 26 solid tumor model, canolol significantly suppressed cyclooxygenase-2 expression; however, no significant tumor growth inhibition was observed, suggesting that canolol preferably shows chemopreventive effects during the stages of initiation/promotion. Canolol may, thus, be considered a potential cancer preventive agent or supplement.Canolol, a phenolic compound obtained from roasted rapeseed oil, shows remarkable therapeutic/protective effect against DSS-induced colitis and the subsequent colon carcinogenesis via its potent chemopreventive antioxidant and anti-inflammatory properties; it is a new phytochemical for inflammation and cancer prevention.
- Subjects
INFLAMMATORY bowel diseases; COLITIS; COLON cancer; CARCINOGENESIS; GUAIACOL; OXIDATIVE stress; CYTOKINES; PREVENTION
- Publication
Carcinogenesis, 2013, Vol 34, Issue 12, p2833
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgt309