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Cepharanthine hydrochloride induces mitophagy targeting GPR30 in hepatocellular carcinoma (HCC).
Wang, Yao; Su, Gui-Feng; Huang, Ze-Xiu; Wang, Zhen-Guang; Zhou, Peng-Jun; Fan, Jiang-Lin; Wang, Yi-Fei.
Affiliation
  • Wang Y; Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, P. R. China.
  • Su GF; Guangzhou Jinan Biomedicine Research and Development Center Co.ltd, Guangzhou, Guangdong, P. R. China.
  • Huang ZX; Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, P. R. China.
  • Wang ZG; Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, P. R. China.
  • Zhou PJ; The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
  • Fan JL; Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou, Guangdong, P. R. China.
  • Wang YF; The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
Expert Opin Ther Targets ; 24(4): 389-402, 2020 04.
Article in En | MEDLINE | ID: mdl-32106726
Objectives: Cepharanthine exhibits a wide range of therapeutic effects against numerous cancers by virtue of its pleiotropic mechanisms. However, cepharanthine monotherapy has insufficient drug efficacy for cancers in animal models and clinical trials. The mechanism of its limited efficacy is unknown.Methods: We investigated the possible mechanism for the limited drug efficacy of cepharanthine in cancer therapy using both hepatocellular carcinoma (HCC) primary cells and cell lines, in vitro and in mouse xenograft models.Results: We found that cepharanthine hydrochloride (CH), a semi-synthetic derivative of cepharanthine, induced mitophagy independent of mTOR signaling, and played an AMPK-dependent protective role in the cell fate of HCC in vitro and in vivo. Mechanistically, we demonstrated that CH may bind to GPR30 receptor to activate the subsequent signal cascade involving mitochondrial fission, thus facilitating mitophagy. Therefore, we proposed a new therapeutic regimen for HCC involving CH combined with an autophagy inhibitor. This regimen exhibited remarkable anti-cancer effects in HCC xenograft mouse model.Conclusion: These results identify CH as a new mitophagy inducer targeting GPR30 receptor. The combination therapy of CH and an autophagy inhibitor may become a novel strategy for enhancing the anti-tumor potential of cepharanthine in HCC.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Hepatocellular / Benzylisoquinolines / Mitophagy / Liver Neoplasms Limits: Adult / Animals / Female / Humans / Male / Middle aged Language: En Journal: Expert Opin Ther Targets Journal subject: TERAPEUTICA Year: 2020 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Hepatocellular / Benzylisoquinolines / Mitophagy / Liver Neoplasms Limits: Adult / Animals / Female / Humans / Male / Middle aged Language: En Journal: Expert Opin Ther Targets Journal subject: TERAPEUTICA Year: 2020 Document type: Article Country of publication: