Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca2+/calmodulin- dependent protein kinase II

Zhipeng Meng, Tao Li, Xiaoxiao Ma, Xiaoqiong Wang, Carl Van Ness, Yichao Gan, Hong Zhou, Jinfen Tang, Guiyu Lou, Yafan Wang, Jun Wu, Yun Yen, Rongzhen Xu, Wendong Huang

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36 Citations (Scopus)

Abstract

Liver cancer is the third leading cause of cancer deaths worldwide but no effective treatment toward liver cancer is available so far. Therefore, there is an unmet medical need to identify novel therapies to efficiently treat liver cancer and improve the prognosis of this disease. Here, we report that berbamine and one of its derivatives, bbd24, potently suppressed liver cancer cell proliferation and induced cancer cell death by targeting Ca2+ /calmodulin-dependent protein kinase II (CAMKII). Furthermore, berbamine inhibited the in vivo tumorigenicity of liver cancer cells in NOD/SCID mice and downregulated the self-renewal abilities of liver cancer-initiating cells. Chemical inhibition or short hairpin RNA-mediated knockdown of CAMKII recapitulated the effects of berbamine, whereas overexpression of CAMKII promoted cancer cell proliferation and increased the resistance of liver cancer cells to berbamine treatments. Western blot analyses of human liver cancer specimens showed that CAMKII was hyperphosphorylated in liver tumors compared with the paired peritumor tissues, which supports a role of CAMKII in promoting human liver cancer progression and the potential clinical use of berbamine for liver cancer therapies. Our data suggest that berbamine and its derivatives are promising agents to suppress liver cancer growth by targeting CAMKII.

Original languageEnglish
Pages (from-to)2067-2077
Number of pages11
JournalMolecular Cancer Therapeutics
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Meng, Z., Li, T., Ma, X., Wang, X., Ness, C. V., Gan, Y., Zhou, H., Tang, J., Lou, G., Wang, Y., Wu, J., Yen, Y., Xu, R., & Huang, W. (2013). Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca2+/calmodulin- dependent protein kinase II. Molecular Cancer Therapeutics, 12(10), 2067-2077. https://doi.org/10.1158/1535-7163.MCT-13-0314