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Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model

View Article: PubMed Central - PubMed

ABSTRACT

Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti-inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti-tumor potential of LFs, and further explore the underlying mechanisms. Firstly, an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was established and administered with or without LFs for 10 weeks, and then the severity of CAC was examined macroscopically and histologically. Subsequently, the effects of LFs on expression of proteins associated with apoptosis and proliferation, levels of inflammatory cytokine, expression of phosphorylated-Janus kinases 2 (p-Jak2) and phosphorylated-signal transducer and activator of transcription 3 (p-Stat3), and activation of nuclear factor-κB (NFκB) and P53 were assessed. We found that LFs could significantly reduce tumorigenesis induced by AOM/DSS. Further study revealed that LFs treatment substantially reduced activation of NFκB and P53, and subsequently suppressed production of inflammatory cytokines and phosphorylation of Jak2 and Stat3 in AOM/DSS-induced mice. Taken together, LFs treatment alleviated AOM/DSS induced CAC via P53 and NFκB/IL-6/Jak2/Stat3 pathways, highlighting the potential of LFs in preventing CAC.

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Effects of LFs on NFκB activation. (A) Immunohistochemical staining of NFκB in colonic tissues; (B,C) Nuclear translocation of NFκB assessed by Western blot and semi-quantitative analysis of these proteins. Nuclear proteins were used to conduct Western blot analysis. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (D,E) Western blot of IKKα/β and p-IκBα expression in colonic tissues and semi-quantitative analysis of these proteins. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control.
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ijms-17-01343-f006: Effects of LFs on NFκB activation. (A) Immunohistochemical staining of NFκB in colonic tissues; (B,C) Nuclear translocation of NFκB assessed by Western blot and semi-quantitative analysis of these proteins. Nuclear proteins were used to conduct Western blot analysis. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (D,E) Western blot of IKKα/β and p-IκBα expression in colonic tissues and semi-quantitative analysis of these proteins. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control.

Mentions: Since nuclear factor-κB (NFκB) activation plays an essential role in modulation of inflammatory cytokines and mediators, we next investigated the activation of NFκB in colon tissues to understand whether NFκB involve in LFs treatment. Initially, NFκB was assessed by IHC analysis, and data in Figure 6A showed that expression of NFκB was markedly elevated in AOM/DSS induced colons, and was substantially decreased by LFs treatment. Western blot analysis showed that LFs significantly reduced nuclear translocation of NFκB (Figure 6B,C).


Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model
Effects of LFs on NFκB activation. (A) Immunohistochemical staining of NFκB in colonic tissues; (B,C) Nuclear translocation of NFκB assessed by Western blot and semi-quantitative analysis of these proteins. Nuclear proteins were used to conduct Western blot analysis. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (D,E) Western blot of IKKα/β and p-IκBα expression in colonic tissues and semi-quantitative analysis of these proteins. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037654&req=5

ijms-17-01343-f006: Effects of LFs on NFκB activation. (A) Immunohistochemical staining of NFκB in colonic tissues; (B,C) Nuclear translocation of NFκB assessed by Western blot and semi-quantitative analysis of these proteins. Nuclear proteins were used to conduct Western blot analysis. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (D,E) Western blot of IKKα/β and p-IκBα expression in colonic tissues and semi-quantitative analysis of these proteins. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control.
Mentions: Since nuclear factor-κB (NFκB) activation plays an essential role in modulation of inflammatory cytokines and mediators, we next investigated the activation of NFκB in colon tissues to understand whether NFκB involve in LFs treatment. Initially, NFκB was assessed by IHC analysis, and data in Figure 6A showed that expression of NFκB was markedly elevated in AOM/DSS induced colons, and was substantially decreased by LFs treatment. Western blot analysis showed that LFs significantly reduced nuclear translocation of NFκB (Figure 6B,C).

View Article: PubMed Central - PubMed

ABSTRACT

Inflammatory bowel disease (IBD) is generally considered as a major risk factor in the progression of colitis-associated carcinogenesis (CAC). Thus, it is well accepted that ameliorating inflammation creates a potential to achieve an inhibitory effect on CAC. Licorice flavonoids (LFs) possess strong anti-inflammatory activity, making it possible to investigate its pharmacologic role in suppressing CAC. The purpose of the present study was to evaluate the anti-tumor potential of LFs, and further explore the underlying mechanisms. Firstly, an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was established and administered with or without LFs for 10 weeks, and then the severity of CAC was examined macroscopically and histologically. Subsequently, the effects of LFs on expression of proteins associated with apoptosis and proliferation, levels of inflammatory cytokine, expression of phosphorylated-Janus kinases 2 (p-Jak2) and phosphorylated-signal transducer and activator of transcription 3 (p-Stat3), and activation of nuclear factor-&kappa;B (NF&kappa;B) and P53 were assessed. We found that LFs could significantly reduce tumorigenesis induced by AOM/DSS. Further study revealed that LFs treatment substantially reduced activation of NF&kappa;B and P53, and subsequently suppressed production of inflammatory cytokines and phosphorylation of Jak2 and Stat3 in AOM/DSS-induced mice. Taken together, LFs treatment alleviated AOM/DSS induced CAC via P53 and NF&kappa;B/IL-6/Jak2/Stat3 pathways, highlighting the potential of LFs in preventing CAC.

No MeSH data available.


Related in: MedlinePlus