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Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)
Published on: September 11, 2012
Citrus limonoids obacunone and limonin inhibit azoxymethane-induced colon carcinogenesis in rats
1Department of Pathology, Kanazawa Medical University, Uchinada, Ishikawa, Japan. takutt@kanazawa-med.ac.jp
Abstract:
Obacunone and limonin are bitter limonoids in citrus. Their modifying effects on the development of aberrant crypt foci (ACF), the activity of detoxification enzymes, glutathione S-transferase (GST) and quinone reductase (QR), and cell proliferation activity were investigated in male F344 rats treated with azoxymethane (AOM). Obacunone and limonin were administered in the diet, during the initiation (for 4 weeks) or postinitiation phase (for 4 weeks) of AOM-induced tumorigenesis. Feeding of obacunone and limonin (0.02% or 0.05%) caused significant reduction (55-65% by "initiation" feeding and 28-42% by "postinitiation" feeding) in the yield of ACF. The ability to reduce the proliferating cell nuclear antigen-labeling index in crypts and correlated well with the prevention of ACF. In a subsequent long-term experiment (38 weeks), in which rats were initiated with AOM and fed 0.05% obacunone or 0.05% limonin during the initiation or post-initiation phase, both compounds in diet caused significant reduction (65%-92% inhibition) in the incidence of colonic adenocarcinoma. Thus, citrus bitter limonoids obacunone and limonin possess chemopreventive effects on chemically induced rat colon carcinogenesis.
Insights
Citrus compounds obacunone and limonin significantly reduced aberrant crypt foci and colon cancer in rats. These bitter limonoids demonstrate chemopreventive potential against chemically induced colon carcinogenesis.
Area of Science:
- Nutritional biochemistry
- Cancer chemoprevention
- Toxicology
Background:
- Aberrant crypt foci (ACF) are early indicators of colon cancer.
- Citrus limonoids, such as obacunone and limonin, are known for their potential biological activities.
- Understanding the chemopreventive effects of dietary compounds is crucial for cancer research.
Purpose of the Study:
- To investigate the chemopreventive effects of obacunone and limonin on azoxymethane (AOM)-induced colon carcinogenesis in rats.
- To evaluate the impact of these limonoids on ACF development, detoxification enzyme activity, and cell proliferation.
Main Methods:
- Male F344 rats were treated with AOM to induce colon tumorigenesis.
- Obacunone and limonin were administered orally during the initiation or post-initiation phases of tumorigenesis.
- Aberrant crypt foci (ACF), proliferating cell nuclear antigen (PCNA)-labeling index, and incidence of colonic adenocarcinoma were assessed.
Main Results:
- Dietary administration of obacunone and limonin significantly reduced the yield of ACF (55-65% during initiation, 28-42% post-initiation).
- Both compounds decreased the PCNA-labeling index, correlating with ACF prevention.
- Long-term feeding (38 weeks) resulted in significant inhibition of colonic adenocarcinoma incidence (65%-92%).
Conclusions:
- Citrus bitter limonoids obacunone and limonin exhibit significant chemopreventive properties against chemically induced colon cancer in a rat model.
- These findings suggest potential therapeutic applications for limonoids in colon cancer prevention strategies.
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