title: Flavonoids Extracted from Licorice Prevents Colitis-Associated Carcinogenesis in AOM/DSS Mouse Model.
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.
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. huoxiaoweiforever@163.com.
authors: Xiaowei
authors: X
authors: Huo
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. liuermengmeng@126.com.
authors: Dongyu
authors: D
authors: Liu
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. mmliu.bio@gmail.com.
authors: Li
authors: L
authors: Gao
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. wangkun000guai@163.com.
authors: Liyong
authors: L
authors: Li
authors: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China. licao2016@126.com.
authors: Li
authors: L
authors: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001397:Azoxymethane / Q000633:toxicity*; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000150:complications* / Q000378:metabolism; D016264:Dextran Sulfate / Q000633:toxicity*; D004195:Disease Models, Animal; D005260:Female; D005419:Flavonoids / Q000737:chemistry* / Q000627:therapeutic use*; D006035:Glycyrrhiza / Q000737:chemistry*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D005419:Flavonoids; D015850:Interleukin-6; D016328:NF-kappa B; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D016264:Dextran Sulfate; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2; D001397:Azoxymethane
keywords: colitis-associated carcinogenesis; inflammatory bowel disease; licorice flavonoids