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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.

No MeSH data available.


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Effects of LFs on phosphorylation of Jak2 and Stat3: (A) Immunohistochemical staining of p-Jak2 and p-Stat3 in colonic tissues; and (B,C) Western blot of p-Jak2 and p-Stat3 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-f005: Effects of LFs on phosphorylation of Jak2 and Stat3: (A) Immunohistochemical staining of p-Jak2 and p-Stat3 in colonic tissues; and (B,C) Western blot of p-Jak2 and p-Stat3 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: To further elucidate the molecular mechanism underlying the anti-tumor effect of LFs, Western blot and IHC analysis were conducted to examine phosphorylation of oncogenic proteins Jak2 and Stat3, well known as downstream of IL-6, which were reported to play critical roles in the progression of CAC using Western blot and IHC analysis. Figure 5A shows representative sections of the expression of p-Jak2 and p-Stat3. The IHC images showed that expression of p-Jak2 and p-Stat3 were elevated in the colon tissues of mice treated with AOM/DSS, which was markedly decreased after mice were treated with LFs. Moreover, Western blot analyses were consistent with IHC evaluation (Figure 5B,C), verifying that high expression of p-Jak2 and p-Stat3 induced by AOM/DSS was substantially suppressed by LFs treatment.


Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model
Effects of LFs on phosphorylation of Jak2 and Stat3: (A) Immunohistochemical staining of p-Jak2 and p-Stat3 in colonic tissues; and (B,C) Western blot of p-Jak2 and p-Stat3 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

License
Show All Figures
getmorefigures.php?uid=PMC5037654&req=5

ijms-17-01343-f005: Effects of LFs on phosphorylation of Jak2 and Stat3: (A) Immunohistochemical staining of p-Jak2 and p-Stat3 in colonic tissues; and (B,C) Western blot of p-Jak2 and p-Stat3 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: To further elucidate the molecular mechanism underlying the anti-tumor effect of LFs, Western blot and IHC analysis were conducted to examine phosphorylation of oncogenic proteins Jak2 and Stat3, well known as downstream of IL-6, which were reported to play critical roles in the progression of CAC using Western blot and IHC analysis. Figure 5A shows representative sections of the expression of p-Jak2 and p-Stat3. The IHC images showed that expression of p-Jak2 and p-Stat3 were elevated in the colon tissues of mice treated with AOM/DSS, which was markedly decreased after mice were treated with LFs. Moreover, Western blot analyses were consistent with IHC evaluation (Figure 5B,C), verifying that high expression of p-Jak2 and p-Stat3 induced by AOM/DSS was substantially suppressed by LFs treatment.

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