title: 4-Chlorbenzoyl Berbamine, a Novel Derivative of the Natural Product Berbamine, Potently Inhibits the Growth of Human Myeloma Cells by Modulating the NF-κB and JNK Signalling Pathways.
abstract: Multiple myeloma (MM) remains incurable despite the development and the use of new agents. In our studies, we found that 4-chlorbenzoyl berbamine (BBMD9), a novel synthetic derivative of berbamine, inhibited the proliferation of MM cells in dose- and time-dependent manners. Flow cytometric (FCM) analysis revealed that MM cells were arrested in the G1 phase and that apoptotic cells increased in a time-dependent manner. Moreover, the BBMD9 treatment downregulated IKKα and IKKβ, inhibited p-IκBα, and blocked p65 nuclear localization. Consistently, NF-κB downstream targets, such as cyclinD1 and survivin, were also reduced. In addition, BBMD9 phosphorylated the activity of JNK and c-Jun.
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Yun
authors: Y
authors: Liang
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Xin
authors: X
authors: He
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Xian
authors: X
authors: Li
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Xuzhao
authors: X
authors: Zhang
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Xiaohong
authors: X
authors: Zhang
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Lei
authors: L
authors: Zhang
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Xi
authors: X
authors: Qiu
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Xiaoying
authors: X
authors: Zhao
authors: a Department of Hematology , The Second Affiliated Hospital of Zhejiang University of Medicine , Hangzhou , Zhejiang , China.
authors: Rongzhen
authors: R
authors: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009101:Multiple Myeloma / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D044182:Benzylisoquinolines; D001688:Biological Products; D016328:NF-kappa B; D048031:JNK Mitogen-Activated Protein Kinases; C027870:berbamine
keywords: JNK; Multiple myeloma; apoptosis; berbamine derivatives; nuclear factor-kappaB