Abstract
The inhibitory effects of exogenous melatonin (MEL) on colon oncogenesis were investigated using an azoxymethane (AOM)/dextran sodium sulfate (DSS) rat model. Male F344 rats initiated with a single intraperitoneal injection of AOM (20mg/kg bw) were promoted by 1% (w/v) DSS in drinking water for 7 days. They were then given 0.4, 2 or 10ppm MEL in drinking water for 17 weeks. At week 20, the development of colonic adenocarcinoma was significantly inhibited by the administration with MEL dose-dependently. MEL exposure modulated the mitotic and apoptotic indices in the colonic adenocarcinomas that developed and lowered the immunohistochemical expression of nuclear factor kappa B, tumor necrosis factor alpha, interleukin-1beta and STAT3 in the epithelial malignancies. These results may indicate the beneficial effects of MEL on colitis-related colon carcinogenesis and a potential application for inhibiting colorectal cancer development in the inflamed colon.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / chemically induced
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Adenocarcinoma / prevention & control*
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Animals
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Azoxymethane / toxicity
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Biomarkers, Tumor / metabolism
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Colon / drug effects
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Colon / metabolism
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Colon / pathology
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Colonic Neoplasms / chemically induced
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Colonic Neoplasms / prevention & control*
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Dextran Sulfate / toxicity
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Dose-Response Relationship, Drug
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Drinking
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Immunohistochemistry
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Injections, Intraperitoneal
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Interleukin-1beta / metabolism
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / pathology
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Male
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Melatonin / pharmacology*
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Mitotic Index
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NF-kappa B / metabolism
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Rats
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Rats, Inbred F344
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STAT3 Transcription Factor / metabolism
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antineoplastic Agents
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Biomarkers, Tumor
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Interleukin-1beta
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NF-kappa B
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STAT3 Transcription Factor
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Stat3 protein, rat
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Tumor Necrosis Factor-alpha
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Dextran Sulfate
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Melatonin
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Azoxymethane