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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 expression of proteins associated with proliferation and apoptosis in colonic tissues: (A) Immunohistochemical staining of Bax, Bcl-2, and PCNA in colonic tissues; (B,C) Western blot of Bax and Bcl-2 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; (D,E) Western blot of PCNA, p-P53, P21, and CyclinD1 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-f003: Effects of LFs on expression of proteins associated with proliferation and apoptosis in colonic tissues: (A) Immunohistochemical staining of Bax, Bcl-2, and PCNA in colonic tissues; (B,C) Western blot of Bax and Bcl-2 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; (D,E) Western blot of PCNA, p-P53, P21, and CyclinD1 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: Uncontrolled proliferation and evasion of apoptosis are considered common events during colon carcinogenesis. Accordingly, we examined protein levels of Bax and Bcl-2, corresponding to apoptosis and expression of proliferating cell nuclear antigen (PCNA), p-P53, P21, and CyclinD1, corresponding to proliferation. IHC analysis demonstrated that the expression of pro-apoptosis protein Bax was elevated in LFs treated group; meanwhile, anti-apoptosis protein Bcl-2 was reduced by LFs treatment (Figure 3A). Western blot analysis confirmed that LFs treatment could substantially increase expression of Bax and reduce levels of Bcl-2 (Figure 3B,C), thus inducing apoptosis of tumors.


Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model
Effects of LFs on expression of proteins associated with proliferation and apoptosis in colonic tissues: (A) Immunohistochemical staining of Bax, Bcl-2, and PCNA in colonic tissues; (B,C) Western blot of Bax and Bcl-2 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; (D,E) Western blot of PCNA, p-P53, P21, and CyclinD1 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-f003: Effects of LFs on expression of proteins associated with proliferation and apoptosis in colonic tissues: (A) Immunohistochemical staining of Bax, Bcl-2, and PCNA in colonic tissues; (B,C) Western blot of Bax and Bcl-2 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; (D,E) Western blot of PCNA, p-P53, P21, and CyclinD1 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: Uncontrolled proliferation and evasion of apoptosis are considered common events during colon carcinogenesis. Accordingly, we examined protein levels of Bax and Bcl-2, corresponding to apoptosis and expression of proliferating cell nuclear antigen (PCNA), p-P53, P21, and CyclinD1, corresponding to proliferation. IHC analysis demonstrated that the expression of pro-apoptosis protein Bax was elevated in LFs treated group; meanwhile, anti-apoptosis protein Bcl-2 was reduced by LFs treatment (Figure 3A). Western blot analysis confirmed that LFs treatment could substantially increase expression of Bax and reduce levels of Bcl-2 (Figure 3B,C), thus inducing apoptosis of tumors.

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