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.

KEYWORDS:

• Multiple myeloma
• berbamine derivatives
• nuclear factor-kappaB
• JNK
• apoptosis

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

 This project was supported by the National Nature Science Foundation of China (No. 81201869), the Nature Science Foundation of Zhejiang Province (No. LQ12H16012), and the Nature Science Foundation of Zhejiang Province (No. LY14H160032).