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. 2018 Feb 12;10(2):202.
doi: 10.3390/nu10020202.

Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice

Kyung-Sook Chung  1 , Se-Yun Cheon  2 , Seong-Soo Roh  3 , Minho Lee  4 , Hyo-Jin An  5
Affiliations

Chemopreventive Effect of Aster glehni on Inflammation-Induced Colorectal Carcinogenesis in Mice

Kyung-Sook Chung et al. Nutrients. .

Abstract

Although Aster glehni is a common dietary herb that has various bioactivities, including anti-diabetic, anti-adipogenic, and anti-inflammatory effects, A. glehni has not been studied in colon cancer. Therefore, we hypothesized the chemopreventive effects of an ethanol extract of A. glehni (AG) on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer (CAC) in mice. In this study, we found that treatment with AG significantly attenuated the AOM/DSS-induced enlargement of the spleen and shortening of the colon. In addition, colonic tumor formation, colonic damage, and increased muscle thickness were significantly reduced in AOM/DSS-induced mice fed AG. Treatment with AG also reduced intestinal interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 protein expression in mice with AOM/DSS-induced CAC. Furthermore, AG reduced nuclear factor (NF)-κB activation via phosphorylation and degradation of inhibitor of kappa Bα (IκBα), leading to inhibition of NF-κB p65 nuclear translocation. It also downregulated the expression of NF-κB-related proteins, including the B-cell lymphoma 2 (Bcl-2) family and inhibitors of apoptosis proteins (IAPs), in mice with AOM/DSS-induced CAC. Taken together, these findings suggest that the treatment with AG inhibited colitis-associated colon carcinogenesis in mice, and this chemopreventive effect was strongly mediated by suppression of the NF-κB signaling pathway, indicating that AG could be a promising protective agent against CAC.

Keywords: Aster glehni; NF-κB; chemoprevention; colitis-associated cancer; inflammation.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schema of the AOM/DSS-induced mice model. AOM/DSS-induced mice were treated with 5-ASA (75 mg/kg/day; i.p.) or AG (25 mg/kg/day; p.o.) as described in Materials and Methods. 5-ASA was used as a reference substance. DW = distilled water
Figure 2
Figure 2
Effect of AG on body weight and spleen weight in AOM/DSS-induced mice. (A) Body weight; (B) spleen weight; and (C) spleen weight (SW)/body weight (BW) were measured at last day of AOM/DSS-treated experiments. Values represent mean ± S.D. of three independent experiments. ### p < 0.001 vs. the control group; ** p < 0.01 vs. the AOM/DSS group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test. Con = Control.
Figure 3
Figure 3
Inhibitory effect of AG on tumor progression in AOM/DSS-exposured mice. (A) Colons were obtained on the last day of AOM/DSS administration; and (B) colon lengths; and (C,D) number of macroscopic tumors were measured. Values represent mean ± S.D. of three independent experiments. ### p < 0.001 vs. the control group; * p < 0.05, ** p < 0.01 and *** p < 0.001 vs. the AOM/DSS group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.
Figure 4
Figure 4
Effect of AG on analysis of colonic section in AOM/DSS-induced mice: (A) H&E staining of colonic section (Original Magnification × 100); and (B) thickness of muscle layer was evaluated using LAS software. Stained section was observed by microscope. Values represent mean ± S.D. of three independent experiments. ### p < 0.001 vs. the control group; *** p < 0.001 vs. the AOM/DSS group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.
Figure 5
Figure 5
Effect of AG on the production of proinflammatory cytokines and the protein expressions in AOM/DSS-induced mice: (A) IL-1β; (B) IL-6 and (C) TNF-α were determined by EIA kits; and (D) Western blot analysis were performed for the protein expression level of iNOS and COX-2 using specific antibodies. Relative ratio level was determined by densitometric analysis (Bio-rad Quantity One® Software) normalized to β-actin. Values represent mean ± S.D. of three independent experiments. # p < 0.05, ### p < 0.001 vs. the control group; ** p < 0.01, *** p < 0.001 vs. the AOM/DSS group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.
Figure 6
Figure 6
Role of AG on the NF-κB pathway in AOM-DSS-induced mice. (A) The nuclear translocation of p65 and expression of p-IκBα and IκBα were determined by Western blot analysis using specific antibodies. Nuclear (N) and cytosol (C) extracts were prepared from colon tissues on the last day of AOM/DSS-treated experiments. Nucleolin, α-tubulin, and β-actin were internal control; (B) NF-κB-related proteins were determined by Western blot analysis using specific antibodies. Relative ratio level was determined by densitometric analysis (Bio-rad Quantity One® Software) normalized to β-actin. Values represent mean ± S.D. of three independent experiments. ## p < 0.01, ### p < 0.001 vs. the control group; * p < 0.05, ** p < 0.01 and *** p < 0.001 vs. the AOM/DSS group; significances between treated groups were determined using ANOVA and Dunnett’s post hoc test.
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