Protection from inflammatory bowel disease and colitis-associated carcinogenesis with 4-vinyl-2,6-dimethoxyphenol (canolol) involves suppression of oxidative stress and inflammatory cytokines.
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.
Research Institute for Drug Delivery System and.
Jun
J
Fang
Takahiro
T
Seki
Tetsuya
T
Tsukamoto
Haibo
H
Qin
Hongzhuan
H
Yin
Long
L
Liao
Hideaki
H
Nakamura
Hiroshi
H
Maeda
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D063646:Carcinogenesis / Q000187:drug effects* / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D016264:Dextran Sulfate / Q000009:adverse effects; D005260:Female; D057809:HEK293 Cells; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008262:Macrophage Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014753:Vinyl Compounds / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D010636:Phenols; D014409:Tumor Necrosis Factor-alpha; D014753:Vinyl Compounds; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C488411:4-vinyl-2,6-dimethoxyphenol