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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.


Related in: MedlinePlus

Effects of LFs on the burden of colonic neoplasms. (A) Microscopic view of colon in mice. AOM/DSS treatment resulted in 100% incidence of colonic neoplasms and no neoplasm was observed in control group; (B) LFs treatment reduced numbers of colonic neoplasms. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (C) Effect of LFs on colon length. Reduced colon length induced by azoxymethane (AOM)/dextran sulfate sodium (DSS) was significantly reversed by LFs treatment. Data are presented as mean ± SD. * p < 0.05 vs. model, ##p < 0.01 vs. vehicle control; (D) Effects of LFs on colon weight to colon length ratio. Colon weight to colon length ratio was assessed after mice were treated with LFs for 10 weeks. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (E) Hematoxylin and eosin (H&E) staining of colons. Histological studies were conducted through hematoxylin and eosin staining. Most colorectal neoplasms were histologically determined as adenoma.
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ijms-17-01343-f002: Effects of LFs on the burden of colonic neoplasms. (A) Microscopic view of colon in mice. AOM/DSS treatment resulted in 100% incidence of colonic neoplasms and no neoplasm was observed in control group; (B) LFs treatment reduced numbers of colonic neoplasms. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (C) Effect of LFs on colon length. Reduced colon length induced by azoxymethane (AOM)/dextran sulfate sodium (DSS) was significantly reversed by LFs treatment. Data are presented as mean ± SD. * p < 0.05 vs. model, ##p < 0.01 vs. vehicle control; (D) Effects of LFs on colon weight to colon length ratio. Colon weight to colon length ratio was assessed after mice were treated with LFs for 10 weeks. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (E) Hematoxylin and eosin (H&E) staining of colons. Histological studies were conducted through hematoxylin and eosin staining. Most colorectal neoplasms were histologically determined as adenoma.

Mentions: Tumor formation was analyzed at the end of the experiment. As shown in Figure 2A,B, in the absence of LFs treatment, AOM/DSS-induced mice exhibited a high tumor burden in the colons, while LFs treatment markedly reduced AOM/DSS-induced tumors. Moreover, decreased colon length was observed in AOM/DSS-induced mice, when compared with the control mice. Such significant decrease was relieved by LFs treatment at 100 mg/kg (Figure 2C). In addition, AOM/DSS treatment could significantly increase colon weight to colon length ratio when compared with mice treated with vehicle control (Figure 2D), which seemed to be a result of apparent mucosal thickening, and LFs treatment significantly decrease this ratio suggesting substantial alleviation of inflammation. Hematoxylin and eosin (H&E) staining of colon tissues was performed in order to analyze the pathology of AOM/DSS-induced colons. The result showed that LFs greatly suppressed the development of CAC induced by AOM/DSS treatment (Figure 2E). These data indicate that LFs exhibits strong suppressive effect on colitis and colorectal tumorigenesis induced by AOM/DSS.


Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model
Effects of LFs on the burden of colonic neoplasms. (A) Microscopic view of colon in mice. AOM/DSS treatment resulted in 100% incidence of colonic neoplasms and no neoplasm was observed in control group; (B) LFs treatment reduced numbers of colonic neoplasms. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (C) Effect of LFs on colon length. Reduced colon length induced by azoxymethane (AOM)/dextran sulfate sodium (DSS) was significantly reversed by LFs treatment. Data are presented as mean ± SD. * p < 0.05 vs. model, ##p < 0.01 vs. vehicle control; (D) Effects of LFs on colon weight to colon length ratio. Colon weight to colon length ratio was assessed after mice were treated with LFs for 10 weeks. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (E) Hematoxylin and eosin (H&E) staining of colons. Histological studies were conducted through hematoxylin and eosin staining. Most colorectal neoplasms were histologically determined as adenoma.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-17-01343-f002: Effects of LFs on the burden of colonic neoplasms. (A) Microscopic view of colon in mice. AOM/DSS treatment resulted in 100% incidence of colonic neoplasms and no neoplasm was observed in control group; (B) LFs treatment reduced numbers of colonic neoplasms. Data are presented as mean ± SD. ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (C) Effect of LFs on colon length. Reduced colon length induced by azoxymethane (AOM)/dextran sulfate sodium (DSS) was significantly reversed by LFs treatment. Data are presented as mean ± SD. * p < 0.05 vs. model, ##p < 0.01 vs. vehicle control; (D) Effects of LFs on colon weight to colon length ratio. Colon weight to colon length ratio was assessed after mice were treated with LFs for 10 weeks. Data are presented as mean ± SD. * p < 0.05, ** p < 0.01 vs. model, ##p < 0.01 vs. vehicle control; (E) Hematoxylin and eosin (H&E) staining of colons. Histological studies were conducted through hematoxylin and eosin staining. Most colorectal neoplasms were histologically determined as adenoma.
Mentions: Tumor formation was analyzed at the end of the experiment. As shown in Figure 2A,B, in the absence of LFs treatment, AOM/DSS-induced mice exhibited a high tumor burden in the colons, while LFs treatment markedly reduced AOM/DSS-induced tumors. Moreover, decreased colon length was observed in AOM/DSS-induced mice, when compared with the control mice. Such significant decrease was relieved by LFs treatment at 100 mg/kg (Figure 2C). In addition, AOM/DSS treatment could significantly increase colon weight to colon length ratio when compared with mice treated with vehicle control (Figure 2D), which seemed to be a result of apparent mucosal thickening, and LFs treatment significantly decrease this ratio suggesting substantial alleviation of inflammation. Hematoxylin and eosin (H&E) staining of colon tissues was performed in order to analyze the pathology of AOM/DSS-induced colons. The result showed that LFs greatly suppressed the development of CAC induced by AOM/DSS treatment (Figure 2E). These data indicate that LFs exhibits strong suppressive effect on colitis and colorectal tumorigenesis induced by AOM/DSS.

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