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Updated: Jun 27, 2026
Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)
Published on: September 11, 2012
Melatonin suppresses AOM/DSS-induced large bowel oncogenesis in rats
Takuji Tanaka1, Yumiko Yasui, Mayu Tanaka
1Department of Oncologic Pathology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa 920-0293, Japan. takutt@kanazawa-med.ac.jp
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.
Insights
Exogenous melatonin (MEL) significantly inhibited colon cancer development in a rat model. Melatonin treatment reduced tumor incidence and modulated key molecular pathways involved in inflammation and cell proliferation, suggesting its potential for colorectal cancer prevention.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Colorectal cancer is a significant global health concern.
- Inflammation plays a crucial role in the development of colon cancer.
- Melatonin, a hormone with antioxidant and anti-inflammatory properties, has shown potential in cancer prevention.
Purpose of the Study:
- To investigate the inhibitory effects of exogenous melatonin (MEL) on colon oncogenesis.
- To evaluate the dose-dependent efficacy of MEL in a colitis-related colorectal cancer model.
- To explore the molecular mechanisms underlying MEL's anti-cancer effects in the colon.
Main Methods:
- Utilized an azoxymethane (AOM)/dextran sodium sulfate (DSS) rat model for colon carcinogenesis.
- Administered varying doses of MEL (0.4, 2, or 10 ppm) in drinking water for 17 weeks.
- Assessed tumor development, mitotic and apoptotic indices, and expression of key inflammatory markers (NF-κB, TNF-α, IL-1β, STAT3).
Main Results:
- MEL administration significantly inhibited the development of colonic adenocarcinoma in a dose-dependent manner.
- MEL modulated mitotic and apoptotic indices within the developing tumors.
- Reduced immunohistochemical expression of NF-κB, TNF-α, IL-1β, and STAT3 was observed in epithelial malignancies following MEL treatment.
Conclusions:
- Exogenous melatonin demonstrates beneficial effects in preventing colitis-related colon carcinogenesis.
- MEL's mechanism involves modulating cell proliferation, apoptosis, and key inflammatory signaling pathways.
- Melatonin holds potential as a therapeutic or preventive agent for colorectal cancer in inflamed colons.
