title: Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling.
abstract: As a traditional anti-inflammatory Chinese herbal medicine, Alkaloid berberine has been recently reported to exhibit anti-tumour effects against a wide spectrum of cancer. However, the mechanism was largely unknown. Gene chip array reveals that with berberine treatment, c-Myc, the target gene of Wnt pathway, was down-regulated 5.3-folds, indicating that berberine might inhibit Wnt signalling. TOPflash analysis revealed that Wnt activity was significantly reduced after berberine treatment, and the mechanism of which might be that berberine disrupted β-catenin transfer to nucleus through up-regulating the expression of adenomatous polyposis coli (APC) gene and stabilized APC-β-catenin complex. Berberine administration in ApcMin/+ mice exhibited fewer and smaller polyps in intestine, along with reduction in cyclin D1 and c-Myc expression. In clinical practice, oral administration of berberine also significantly reduced the familial adenomatous polyposis patients' polyp size along with the inhibition of cyclin D1 expression in polyp samples. These observations indicate that berberine inhibits colon tumour formation through inhibition of Wnt/β-catenin signalling and berberine might be a promising drug for the prevention of colon cancer.
authors.affiliation: Cancer Research Center, Xiamen University Medical College, Xiamen, China; School of life Science, Xiamen University, Xiamen, China.
authors.forename: Junfang
authors.initials: J
authors.lastname: Zhang
authors.forename: Hailong
authors.initials: H
authors.lastname: Cao
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.forename: Hanwei
authors.initials: H
authors.lastname: Cao
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Xu
authors.forename: Hang
authors.initials: H
authors.lastname: Ruan
authors.forename: Tingting
authors.initials: T
authors.lastname: Yi
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.forename: Rui
authors.initials: R
authors.lastname: Qu
authors.forename: Gang
authors.initials: G
authors.lastname: Song
authors.forename: Bangmao
authors.initials: B
authors.lastname: Wang
authors.forename: Tianhui
authors.initials: T
authors.lastname: Hu
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000188:drug therapy* / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D021381:Protein Transport; D015854:Up-Regulation / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D016588:Anticarcinogenic Agents; C495267:CTNNB1 protein, mouse; D051176:beta Catenin; D001599:Berberine
keywords: Wnt; berberine; colon cancer; familial adenomatous polyposis; signal transduction
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