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Research ArticleArticle

Tetrandrine Inhibits Wnt/β-Catenin Signaling and Suppresses Tumor Growth of Human Colorectal Cancer

Bai-Cheng He, Jian-Li Gao, Bing-Qiang Zhang, Qing Luo, Qiong Shi, Stephanie H. Kim, Enyi Huang, Yanhong Gao, Ke Yang, Eric R. Wagner, Linyuan Wang, Ni Tang, Jinyong Luo, Xing Liu, Mi Li, Yang Bi, Jikun Shen, Gaurav Luther, Ning Hu, Qixin Zhou, Hue H. Luu, Rex C. Haydon, Yingming Zhao and Tong-Chuan He
Molecular Pharmacology February 2011, 79 (2) 211-219; DOI: https://doi.org/10.1124/mol.110.068668
Bai-Cheng He
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Jian-Li Gao
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Bing-Qiang Zhang
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Qing Luo
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Qiong Shi
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Stephanie H. Kim
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Enyi Huang
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Yanhong Gao
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Ke Yang
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Eric R. Wagner
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Linyuan Wang
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Ni Tang
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Jinyong Luo
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Xing Liu
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Mi Li
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Yang Bi
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Jikun Shen
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Gaurav Luther
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Ning Hu
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Qixin Zhou
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This article has a correction. Please see:

  • Correction to “Tetrandrine Inhibits Wnt/β-Catenin Signaling and Suppresses Tumor Growth of Human Colorectal Cancer” - March 01, 2011

Abstract

As one of the most common malignancies, colon cancer is initiated by abnormal activation of the Wnt/β-catenin pathway. Although the treatment options have increased for some patients, overall progress has been modest. Thus, there is a great need to develop new treatments. We have found that bisbenzylisoquinoline alkaloid tetrandrine (TET) exhibits anticancer activity. TET is used as a calcium channel blocker to treat hypertensive and arrhythmic conditions in Chinese medicine. Here, we investigate the molecular basis underlying TET's anticancer activity. We compare TET with six chemotherapy drugs in eight cancer lines and find that TET exhibits comparable anticancer activities with camptothecin, vincristine, paclitaxel, and doxorubicin, and better than that of 5-fluorouracil (5-FU) and carboplatin. TET IC50 is ≤5 μM in most of the tested cancer lines. TET exhibits synergistic anticancer activity with 5-FU and reduces migration and invasion capabilities of HCT116 cells. Furthermore, TET induces apoptosis and inhibits xenograft tumor growth of colon cancer. TET treatment leads to a decrease in β-catenin protein level in xenograft tumors, which is confirmed by T-cell factor/lymphocyte enhancer factor and c-Myc reporter assays. It is noteworthy that HCT116 cells with allelic oncogenic β-catenin deleted are less sensitive to TET-mediated inhibition of proliferation, viability, and xenograft tumor growth. Thus, our findings strongly suggest that the anticancer effect of TET in colon cancer may be at least in part mediated by targeting β-catenin activity. Therefore, TET may be used alone or in combination as an effective anticancer agent.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was supported in part by the National Institutes of Health National Cancer Institute [Grant CA106569]; the National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases [Grants AR50142, AR054381]; the National Institutes of Health National Center for Complementary and Alternative Medicine [Grant AT004418]; and the National Basic Research Program of China [Grant 2011CB70790].

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.068668.

  • ABBREVIATIONS:

    VP-16
    etoposide
    VM-26
    teniposide
    5-FU
    5-fluorouracil
    DMSO
    dimethyl sulfoxide
    EGFP
    enhanced green fluorescence protein
    MTT
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
    PBS
    phosphate-buffered saline
    TCF/LEF
    T-cell factor/lymphocyte enhancer factor
    TET
    tetrandrine
    PI
    propidium iodide.

  • Received September 4, 2010.
  • Accepted October 22, 2010.
  • Copyright © 2011 The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 79 (2)
Molecular Pharmacology
Vol. 79, Issue 2
1 Feb 2011
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Research ArticleArticle

Tetrandrine Inhibits Wnt/β-Catenin Signaling and Suppresses Tumor Growth of Human Colorectal Cancer

Bai-Cheng He, Jian-Li Gao, Bing-Qiang Zhang, Qing Luo, Qiong Shi, Stephanie H. Kim, Enyi Huang, Yanhong Gao, Ke Yang, Eric R. Wagner, Linyuan Wang, Ni Tang, Jinyong Luo, Xing Liu, Mi Li, Yang Bi, Jikun Shen, Gaurav Luther, Ning Hu, Qixin Zhou, Hue H. Luu, Rex C. Haydon, Yingming Zhao and Tong-Chuan He
Molecular Pharmacology February 1, 2011, 79 (2) 211-219; DOI: https://doi.org/10.1124/mol.110.068668

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Research ArticleArticle

Tetrandrine Inhibits Wnt/β-Catenin Signaling and Suppresses Tumor Growth of Human Colorectal Cancer

Bai-Cheng He, Jian-Li Gao, Bing-Qiang Zhang, Qing Luo, Qiong Shi, Stephanie H. Kim, Enyi Huang, Yanhong Gao, Ke Yang, Eric R. Wagner, Linyuan Wang, Ni Tang, Jinyong Luo, Xing Liu, Mi Li, Yang Bi, Jikun Shen, Gaurav Luther, Ning Hu, Qixin Zhou, Hue H. Luu, Rex C. Haydon, Yingming Zhao and Tong-Chuan He
Molecular Pharmacology February 1, 2011, 79 (2) 211-219; DOI: https://doi.org/10.1124/mol.110.068668
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