Abstract
Background: Tussilagone, a major component of Tussilago farfara L., has anti-angiogenic and anti-inflammatory effects. However, the therapeutic and preventive activity of tussilagone in colitis-associated colon carcinogenesis is unknown. Methods: We intended to investigate the therapeutic effects and the potential mechanism of action underlying the pharmacological activity of tussilagone on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). We injected BALB/c mice with AOM and administered 2% DSS in drinking water. The mice were given tussilagone (2.5 and 5 mg/kg body weight) and colon tissues was collected at 72 days. We used Western blotting, immunohistochemistry and real-time RT-PCR analyses to examine the tumorigenesis and inflammatory status of the colon. Results: Tussilagone administration significantly reduced the formation of colonic tumors. In addition, tussilagone treatment markedly reduced the inflammatory mediators and increased heme oxygease-1 in protein and mRNA levels in colon tissues. Meanwhile, nuclear NF-κB-positive cells were elevated and nuclear Nrf2-positive cells were demised by tussilagone treatment in colon tissues. Tussilagone also reduced cell proliferation, induced apoptosis and decreased the β-catenin expression. Conclusions: Tussilagone administration decreases the inflammation and proliferation induced by AOM/DSS and induced apoptosis in colon tissue. Overall, this study indicates the potential value of tussilagone in suppressing colon tumorigenesis.
Highlights
Colon cancer is the third most prevalent malignancy worldwide and is the fourth most common cause of cancer-related death [1]
Since our previous study showed that tussilagone has anti-inflammatory activity at doses ranging from 0.5 to 2.5 mg/kg, we decided to provide a similar dose of tussilagone in this study
Since the AOM/dextran sulphate sodium (DSS)-induced colon-cancer model is deeply related to inflammatory response, we examined whether the suppression of colon tumorigenesis by tussilagone treatment is associated with anti-inflammatory activity via the regulation of pro-inflammatory mediators, including pro-inflammatory cytokines, in colon tissues
Summary
Colon cancer is the third most prevalent malignancy worldwide and is the fourth most common cause of cancer-related death [1]. Common risk factors for colon cancer include genetic background and environmental risk factors, such as diabetes, cholecystectomy, obesity and high-fat diets [3]. Among these factors, long standing inflammatory bowel disease (IBD) is a higher risk for developing colon cancer [4,5,6]. Methods: We intended to investigate the therapeutic effects and the potential mechanism of action underlying the pharmacological activity of tussilagone on colitis-associated colon cancer induced in mice using azoxymethane (AOM)/dextran sulfate sodium (DSS). Conclusions: Tussilagone administration decreases the inflammation and proliferation induced by AOM/DSS and induced apoptosis in colon tissue. This study indicates the potential value of tussilagone in suppressing colon tumorigenesis
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