Berberine potently attenuates intestinal polyps growth in ApcMin mice and familial adenomatous polyposis patients through inhibition of Wnt signalling

Authors

  • Junfang Zhang,

    1. Cancer Research Center, Xiamen University Medical College, Xiamen, China
    2. School of life Science, Xiamen University, Xiamen, China
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Hailong Cao,

    1. Department of Gastroenterology, General Hospital, Tianjin Medical University, Tianjin, China
    Search for more papers by this author
    • These authors contributed equally to this work.
  • Bing Zhang,

    1. Department of Basic Medicine, Xiamen University Medical College, Xiamen, China
    Search for more papers by this author
  • Hanwei Cao,

    1. Cancer Research Center, Xiamen University Medical College, Xiamen, China
    Search for more papers by this author
  • Xiuqin Xu,

    1. Department of Basic Medicine, Xiamen University Medical College, Xiamen, China
    2. Institute of Stem Cell and Regenerative Medicine, Xiamen University Medical College, Xiamen, China
    Search for more papers by this author
  • Hang Ruan,

    1. Cancer Research Center, Xiamen University Medical College, Xiamen, China
    Search for more papers by this author
  • Tingting Yi,

    1. Cancer Research Center, Xiamen University Medical College, Xiamen, China
    Search for more papers by this author
  • Li Tan,

    1. Cancer Research Center, Xiamen University Medical College, Xiamen, China
    Search for more papers by this author
  • Rui Qu,

    1. Department of Gastroenterology, General Hospital, Tianjin Medical University, Tianjin, China
    Search for more papers by this author
  • Gang Song,

    Corresponding author
    1. Cancer Research Center, Xiamen University Medical College, Xiamen, China
    • Correspondence to: Tianhui HU, Ph.D., Gang SONG, Ph.D., Cancer Research Center, Xiamen University Medical College, Xiamen 361005, China.

      Tel.: +86 592 2188223

      Fax: +86 592 2186731

      E-mails: thu@xmu.edu.cn, gangsongsd@xmu.edu.cn

      or

      Bangmao WANG, M.D., Department of Gastroenterology, General Hospital, Tianjin Medical University, Tianjin 300052, China.

      Tel.: +86 22 60362608

      Fax: +86 22 27813550

      E-mail: gi.tmuh@yeah.net

    Search for more papers by this author
  • Bangmao Wang,

    Corresponding author
    1. Department of Gastroenterology, General Hospital, Tianjin Medical University, Tianjin, China
    • Correspondence to: Tianhui HU, Ph.D., Gang SONG, Ph.D., Cancer Research Center, Xiamen University Medical College, Xiamen 361005, China.

      Tel.: +86 592 2188223

      Fax: +86 592 2186731

      E-mails: thu@xmu.edu.cn, gangsongsd@xmu.edu.cn

      or

      Bangmao WANG, M.D., Department of Gastroenterology, General Hospital, Tianjin Medical University, Tianjin 300052, China.

      Tel.: +86 22 60362608

      Fax: +86 22 27813550

      E-mail: gi.tmuh@yeah.net

    Search for more papers by this author
  • Tianhui Hu

    Corresponding author
    1. Cancer Research Center, Xiamen University Medical College, Xiamen, China
    • Correspondence to: Tianhui HU, Ph.D., Gang SONG, Ph.D., Cancer Research Center, Xiamen University Medical College, Xiamen 361005, China.

      Tel.: +86 592 2188223

      Fax: +86 592 2186731

      E-mails: thu@xmu.edu.cn, gangsongsd@xmu.edu.cn

      or

      Bangmao WANG, M.D., Department of Gastroenterology, General Hospital, Tianjin Medical University, Tianjin 300052, China.

      Tel.: +86 22 60362608

      Fax: +86 22 27813550

      E-mail: gi.tmuh@yeah.net

    Search for more papers by this author

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.

Ancillary