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

Liang, Yun; He, Xin; Li, Xian; Zhang, Xuzhao; Zhang, Xiaohong; Zhang, Lei; Qiu, Xi; Zhao, Xiaoying; Xu, Rongzhen

doi:10.1080/07357907.2016.1235709

Cited by 16 publications

(11 citation statements)

References 37 publications

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“… 13 , 16 Some studies report that BBM exerts its anticancer effect through inducing apoptosis, which is mediated by the regulation of various pathways, such as JNK/AP-1, Calmodulin-dependent protein kinase II and smad3 pathways. 13 , 17 , 18 Moreover, a literature search in the database indicates that there are some studies focusing on the chemosensitization effect of BBM. BBM and its derivatives could enhance the antitumor effect of paclitaxel, docetaxel and gemcitabine.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo superior radiosensitizing effect of berbamine for head and neck squamous cell carcinoma

Zhu

Ruan

Feng

et al. 2018

OTT

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BackgroundBerbamine (BBM), one of the bis-benzylisoquinoline products isolated from Berberis amurensis, has been demonstrated for its anticancer effect against leukemia, breast cancer, liver cancer, etc. There are some studies focusing on the chemosensitization effect of BBM. However, there is no report about whether BBM could enhance the anticancer effect of radiation, which made us to explore the possible radiosensitization effect of BBM.Materials and methodsHere, in vitro cytotoxicity of BBM was evaluated on two kinds of head and neck squamous cancer cell lines. Clonogenic assay was performed to study the radiosensitization effect of BBM. Western blot was utilized to elucidate the possible mechanism underlying the radiosensitization effect.ResultsBBM effectively inhibited the growth of two kinds of cancer cells in a time- and dose-dependent manner. Radiation plus BBM led to significantly more reduction of the colony-forming ability of cancer cells when compared with radiation alone. BBM plus radiation led to the most reduction of STAT3 phosphorylation, followed by the significant decrease of the ratio of Bax/Bcl-2. In vivo study demonstrated that the combinational administration of BBM and radiation generated the most significant tumor-delaying effect among all of the treatment regimens.ConclusionWe reported, in the current study, the potential role of BBM in not only treating cancer by itself but also offering a promising way to improve the efficacy of radiotherapy by inhibiting the activation of STAT3 and subsequently inducing the apoptosis of cancer.

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo superior radiosensitizing effect of berbamine for head and neck squamous cell carcinoma

Zhu

Ruan

Feng

et al. 2018

OTT

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“…Xu et al ( 36 ) showed that the berbamine derivatives affect the Ca 2+ -stimulated Mg 2+ -dependent ATPase in erythrocyte membranes. Liang et al ( 37 ) reported that 4-chlorbenzoyl berbamine as a novel derivative of berbamine, could inhibit the growth of human myeloma cells by modulating the NF-κB and JNK signaling pathway. Meanwhile, a few previously published studies ( 15 , 24 , 25 ) also reported the berbamine induced SMMC-7721 cell apoptosis in the other signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

Berbamine induces SMMC-7721 cell apoptosis via upregulating p53, downregulating survivin expression and activating mitochondria signaling pathway

Cao

Wang

et al. 2017

Exp Ther Med

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Hepatocellular carcinoma (HCC) is a primary malignancy in the liver, which is a global health problem. The present study aimed to observe the apoptotic effects of berbamine on SMMC-7721 cell lines and to investigate the effects of berbamine on induction of the intrinsic apoptotic pathway. The human HCC SMMC-7721 cells were cultured and cell morphology observed using a phase contrast microscope. SMMC-7721 cell apoptosis was examined by employing a flow cytometry assay. The nuclei of SMMC-7721 cells were stained with DAPI and observed by utilizing a laser fluorescence microscope. Cytochrome c (Cyto c) levels were evaluated by using immunofluorescence staining. The reverse transcription-semi-quantitative polymerase chain reaction (RT-sqPCR) and western blot analysis were used to examine the mRNA and protein levels of B-cell lymphoma 2, (Bcl-2), Bax, Bcl-2-associated X, apoptosis regulator, p53 and survivin, respectively. Berbamine inhibited SMMC-7721 cell growth at 20 and 0 µmol/l, compared with control group (0 µmol/l berbamine). DAPI results demonstrated that berbamine affected the nucleus morphology of SMMC-7721 cells. Berbamine at a concentration of 20 µmol/l (P<0.05) and 40 µmol/l (P<0.01) significantly enhanced apoptosis rate compared with control group. Berbamine triggered Cyto c release from SMMC-7721 cell nuclei to the cytoplasm. Berbamine (10, 20, 40 µmol/l) significantly enhanced Bax and p53 levels and decreased Bcl-2 and survivin levels compared with control group, according to RT-sqPCR and western blot assay findings. In conclusion, berbamine induced SMMC-7721 cell apoptosis, through upregulating p53 expression and downregulating survivin expression, which further triggered mitochondria signaling pathway-mediated apoptosis.

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“…Previous studies have demonstrated that the antitumor effects of BBM in a variety of tumors, including breast cancer [19], myeloma [7,20], hepatoma [9,21], prostatic neoplasms [9], pancreatic carcinoma [22] and lung cancer [23]. Jin [22] con rmed that BBM signi cantly downregulated the expression of the antiapoptotic proteins such as Bcl-2 and Bcl-xL and inhibited proliferation in pancreatic carcinoma cells.…”

Section: Discussionmentioning

confidence: 97%

Berbamine Inhibits Cell Proliferation, Migration, and Invasion and Induces Cell Apoptosis of A549 Cells Via Regulating C-Maf, PI3K/Akt and MDM2-P53 Pathways

Liu

Zhang²,

et al. 2020

Preprint

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Background To investigate the influences of berbamine (BBM) on the cell viability, proliferation, and migration of A549 cells in vitro and in vivo, and explore the possible mechanisms.MethodsAfter the A549 cells were treated with BBM, the cell viability and proliferation of the cancer cells were detected by MTT assay, EdU assay, and colony formation assay. Migration and invasion of cancer cells were illustrated through wound scratch assay and transwell assay. Apoptosis of cancer cells was evaluated by trypan blue dye exclusion assay and elisa assay. Beside, the expression of PI3K/Akt signal pathway-related proteins and c-Maf were detected employing western blotting assay. Xenografted model of NSCLC was used to detect the effect of BBM on tumor growth and metastasis in vivo.ResultsMTT assay showed that BBM inhibited the viability of A549 cells in a concentration-dependent manner and time-dependent manner. The results from the colony formation assay and EdU assay revealed that BBM (10 µM) could significantly inhibit the proliferation of A549 cells (P＜0.001). And BBM (10 µM) significantly inhibited the migration and invasion in the wound scratch assay and transwell assay (P＜0.05). Trypan blue assay and elisa assay indicated that BBM (20 µM) significantly induced apoptosis of A549 cells. The nude mice assay manifested the tumor volume was significantly shrank by BBM (20 mg/kg) (P＜0.05). Western blotting assay showed that the PI3K/Akt and MDM2-p53 signaling pathways were inhibited by BBM, and the expression of c-Maf was downregulated by BBM. ConclusionsBBM could inhibit the proliferation and metastasis, and induce apoptosis of A549 cells in vitro and in vivo, these effects may be achieved by reducing the expression of c-Maf and regulating the PI3K/Akt and MDM2-p53 pathways.

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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

Cited by 16 publications

References 37 publications

In vitro and in vivo superior radiosensitizing effect of berbamine for head and neck squamous cell carcinoma

In vitro and in vivo superior radiosensitizing effect of berbamine for head and neck squamous cell carcinoma

Berbamine induces SMMC-7721 cell apoptosis via upregulating p53, downregulating survivin expression and activating mitochondria signaling pathway

Berbamine Inhibits Cell Proliferation, Migration, and Invasion and Induces Cell Apoptosis of A549 Cells Via Regulating C-Maf, PI3K/Akt and MDM2-P53 Pathways

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