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Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer.

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-?B-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 ?-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.

SUBMITTER: Nam SH

PROVIDER: S-EPMC7235727 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer.

Nam Sang-Hyeon SH Kim Jin-Kyung JK

Biomedicines 20200411 4

<h4>Background</h4>Tussilagone, a major component of <i>Tussilago farfara</i> L., has anti-angiogenic and anti-inflammatory effects. However, the therapeutic and preventive activity of tussilagone in colitis-associated colon carcinogenesis is unknown.<h4>Methods</h4>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 sulfa ...[more]

PMID: 32290483

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Project description:Chronic inflammation is known to promote carcinogenesis; Dicer heterozygous mice are more likely to develop colitis-associated tumors. This study investigates whether Dicer is downregulated in inflamed colon tissues before malignancy occurs and whether increasing Dicer expression in inflamed colon tissues can alleviate colitis and prevent colitis-associated tumorigenesis. Methods: Gene expression in colon tissues was analyzed by immunohistochemistry, immunoblots, and real-time RT-PCR. Hydrogen peroxide or N-acetyl-L-cysteine was used to induce or alleviate oxidative stress, respectively. Mice were given azoxymethane followed by dextran sulfate sodium to induce colitis and colon tumors. Berberine, anastrozole, or pranoprofen was used to rescue Dicer expression in inflammatory colon tissues. Results: Oxidative stress repressed Dicer expression in inflamed colon tissues by inducing miR-215 expression. Decreased Dicer expression increased DNA damage and cytosolic DNA and promoted interleukin-6 expression upon hydrogen peroxide treatment. Dicer overexpression in inflamed colon tissues alleviated inflammation and repressed colitis-associated carcinogenesis. Furthermore, we found that anastrozole, berberine, and pranoprofen could promote Dicer expression and protect cells from hydrogen peroxide-induced DNA damage, thereby reducing cytosolic DNA and partially repressing interleukin-6 expression upon hydrogen peroxide treatment. Rescuing Dicer expression using anastrozole, berberine, or pranoprofen in inflamed colon tissues alleviated colitis and prevented colitis-associated tumorigenesis. Conclusions: Dicer was downregulated in inflamed colon tissues before malignancy occurred. Decreased Dicer expression further exaggerated inflammation, which may promote carcinogenesis. Anastrozole, berberine, and pranoprofen alleviated colitis and colitis-associated tumorigenesis by promoting Dicer expression. Our study provides insight into potential colitis treatment and colitis-associated colon cancer prevention strategies.

Dataset Information

Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer.

Publications

Tussilagone Reduces Tumorigenesis by Diminishing Inflammation in Experimental Colitis-Associated Colon Cancer.

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