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Updated: Jun 9, 2026
Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)
Published on: September 11, 2012
Inhibitory effect of silibinin against azoxymethane-induced colon tumorigenesis in A/J mice
Kameswaran Ravichandran1, Balaiya Velmurugan, Mallikarjuna Gu
1Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Denver, Aurora, Colorado 80045, USA.
Purpose:
Colorectal cancer is the second leading cause of cancer-associated deaths, which suggests that more effort is needed to prevent/control this disease. Herein, for the first time, we investigate in vivo the efficacy of silibinin against azoxymethane-induced colon tumorigenesis in A/J mice.
Experimental Design:
Five-week-old male mice were gavaged with vehicle or silibinin (250 and 750 mg/kg) for 25 weeks starting 2 weeks before initiation with azoxymethane (pretreatment regime) or for 16 weeks starting 2 weeks after the last azoxymethane injection (posttreatment regime). The mice were then sacrificed, and colon tissues were examined for tumor multiplicity and size, and molecular markers for proliferation, apoptosis, inflammation, and angiogenesis.
Results:
Silibinin feeding showed a dose-dependent decrease in azoxymethane-induced colon tumorigenesis with stronger efficacy in pretreatment versus posttreatment regimen. Mechanistic studies in tissue samples showed that silibinin inhibits cell proliferation as evident by a decrease (P < 0.001) in proliferating cell nuclear antigen and cyclin D1, and increased Cip1/p21 levels. Silibinin also decreased (P < 0.001) the levels of inducible nitric oxide synthase, cyclooxygenase-2, and vascular endothelial growth factor, suggesting its anti-inflammatory and antiangiogenic potential in this model. Further, silibinin increased cleaved caspase-3 and poly(ADP-ribose) polymerase levels, indicating its apoptotic effect. In other studies, colonic mucosa and tumors expressed high levels of β-catenin, insulin-like growth factor-1 receptorβ, phospho Glycogen synthase kinase-3β, and phospho protein kinase B/pAkt proteins in azoxymethane-treated mice, which were strongly lowered (P < 0.001) by silibinin treatment. Moreover, azoxymethane reduced insulin-like growth factor binding protein-3 protein level, which was enhanced by silibinin.
Conclusions:
Silibinin targets β-catenin and IGF-1Rβ pathways for its chemopreventive efficacy against azoxymethane-induced colon carcinogenesis in A/J mice. Overall, these results support the translational potential of silibinin in colorectal cancer chemoprevention.
Insights
Silibinin effectively prevents colon cancer in mice by reducing tumor growth and targeting key molecular pathways. This study highlights silibinin
Area of Science:
- Oncology
- Chemoprevention
- Molecular Biology
Background:
- Colorectal cancer is a leading cause of cancer deaths globally.
- Effective chemoprevention strategies are crucial for disease control.
- Silibinin, a compound from milk thistle, shows potential anticancer properties.
Purpose of the Study:
- To evaluate the efficacy of silibinin against azoxymethane-induced colon tumorigenesis in a mouse model.
- To investigate the molecular mechanisms underlying silibinin's chemopreventive effects.
Main Methods:
- A/J mice were treated with azoxymethane and varying doses of silibinin (pretreatment or posttreatment).
- Colon tissues were analyzed for tumor development, cell proliferation, apoptosis, inflammation, and angiogenesis markers.
- Key signaling pathways, including β-catenin and IGF-1Rβ, were assessed.
Main Results:
- Silibinin demonstrated a dose-dependent reduction in colon tumor multiplicity and size.
- It inhibited cell proliferation and angiogenesis while promoting apoptosis.
- Silibinin modulated key pathways such as β-catenin and insulin-like growth factor-1 receptor (IGF-1Rβ).
Conclusions:
- Silibinin exhibits significant chemopreventive effects against colon carcinogenesis in mice.
- The compound targets the β-catenin and IGF-1Rβ pathways.
- These findings support the potential of silibinin for colorectal cancer chemoprevention.
