title: Berbamine inhibits the growth of liver cancer cells and cancer-initiating cells by targeting Ca²⁺/calmodulin-dependent protein kinase II.
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 Ca(2+)/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. Mol Cancer Ther; 12(10); 2067-77. ©2013 AACR.
authors: Corresponding Authors: Wendong Huang, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010. whuang@coh.org.
authors: Zhipeng
authors: Z
authors: Meng
authors: Tao
authors: T
authors: Li
authors: Xiaoxiao
authors: X
authors: Ma
authors: Xiaoqiong
authors: X
authors: Wang
authors: Carl
authors: C
authors: Van Ness
authors: Yichao
authors: Y
authors: Gan
authors: Hong
authors: H
authors: Zhou
authors: Jinfen
authors: J
authors: Tang
authors: Guiyu
authors: G
authors: Lou
authors: Yafan
authors: Y
authors: Wang
authors: Jun
authors: J
authors: Wu
authors: Yun
authors: Y
authors: Yen
authors: Rongzhen
authors: R
authors: Xu
authors: Wendong
authors: W
authors: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000008:administration & dosage*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D044182:Benzylisoquinolines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C027870:berbamine
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