A novel synthetic derivative of the natural product berbamine inhibits cell viability and induces apoptosis of human osteosarcoma cells, associated with activation of JNK/AP-1 signaling

Yang, Fan; Nam, Sangkil; Zhao, Robin; Tian, Yuan; Liu, Lucy; Horne, David; Jove, Richard

doi:10.4161/cbt.26045

Cited by 27 publications

(20 citation statements)

References 30 publications

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“… 13 , 20 Some groups synthesized novel BBM derivatives to improve the antitumor efficacy. 16 , 22 In the current study, XTT assay showed that the IC50 of BBM on cancer cells is around 8.3 µg/mL, which is in accordance with previous studies. One of the most important findings in the present study is the radiosensitization effect of BBM.…”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

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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“…The AP‐1 controls gene expression in response to various stimuli, including cytokines, growth factors, stress, and bacterial and viral infections (Xiang et al ., ). The AP‐1 regulates a number of cellular processes including cell proliferation, differentiation, and apoptosis (Yang et al ., ). Recent clinical studies have implicated the constitutive activation of transcription factors AP‐1 in the RCC cells (Hong et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Korean Red Ginseng Extract Enhances the Anticancer Effects of Sorafenib through Abrogation of CREB and c‐Jun Activation in Renal Cell Carcinoma

Chulwon

Lee

Baek

et al. 2017

Phytotherapy Research

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Although application of sorafenib in the treatment of human renal cell carcinoma (RCC) remains one of the best examples of successful targeted therapy, majority of RCC patients suffer from its side effects as well as develop resistance to this targeted therapy. Thus, there is a need to promote novel alternative therapies for the treatment of RCC. In this study, we investigated whether Korean red ginseng extract (KRGE) could inhibit the proliferation and induce chemosensitization in human renal cancer cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after KRGE and sorafenib combination treatment. Korean red ginseng extract suppressed the proliferation of two RCC cell lines; activated caspase-3; caused poly(ADP-ribose) polymerase cleavage; abrogated the expression of B-cell lymphoma 2, B-cell lymphoma extra large, survivin, inhibitors of apoptosis proteins-1/2, cyclooxygenase-2, cyclin D1, matrix metallopeptidase-9, and vascular endothelial growth factor; and upregulated pro-apoptotic gene products. Interestingly, KRGE enhanced the cytotoxic and apoptotic effects of sorafenib in RCC cells. The combination treatment of KRGE and sorafenib more clearly suppressed cyclic adenosine monophosphate response element-binding protein and c-Jun phosphorylation and induced phosphorylation of p53 than did the individual treatment regimen. Our results clearly demonstrate that KRGE can enhance the anticancer activity of sorafenib and may have a substantial potential in the treatment of RCC. Copyright © 2017 John Wiley & Sons, Ltd.

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“…This transcription factor is implicated in the activator protein-1 (AP-1)/COX-2/PGE2 axis, and may play a relevant role in patients with high expression levels of COX-2. The AP-1 complex consist of homo or heterodimers of members of the Jun and Fos families, and affects proliferation, transformation, differentiation, stress response and apoptosis, depending on the composition of the complex, type of cell and microenvironment (20)(21)(22). In addition, FosB overexpression has been reported to induce malignant cell transformation in vitro and in vivo (23).…”

Section: Introductionmentioning

confidence: 99%

FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

2017

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Abstract. The expression levels of cyclooxygenase (COX)-2 and the prostaglandin E2 (PGE2) content have been associated with poor prognosis in patients with colorectal cancer (CRC). There is a strong correlation between COX-2 expression and PGE2 production in tissues from CRC patients, suggesting an important role for COX-2 on the regulation of PGE2 production. Previous studies by the present authors, where CRC patients were divided into high-or low-COX-2 expressing tumors, displayed important differences in the expression levels of several transcription factors involved in carcinogenesis. Among them, FBJ murine osteosarcoma viral oncogene homolog B (FosB), which is a member of the activator protein-1 complex, was the highest upregulated transcription factor in patients with high expression levels of COX-2. The present study aimed to investigate the role of FosB on the COX-2/PGE2 axis in CRC cells with high COX-2 expression levels. Interference RNA technology was used to knockdown FosB expression in HCA-7 cells, and 72 h later the messenger (m)RNA expression levels of COX-1 and COX-2, as well as the PGE2 content, were measured. The results indicated that FosB knockdown decreased the expression levels of COX-2 but did not affect the PGE2 content or the mRNA expression levels of COX-1. The present findings suggest an important role for FosB on the regulation of COX-2 expression, but no effect on the regulation of the PGE2 levels. In addition, the present results imply independent regulatory mechanisms for COX-2 expression and PGE2 content.

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A novel synthetic derivative of the natural product berbamine inhibits cell viability and induces apoptosis of human osteosarcoma cells, associated with activation of JNK/AP-1 signaling

Cited by 27 publications

References 30 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

Korean Red Ginseng Extract Enhances the Anticancer Effects of Sorafenib through Abrogation of CREB and c‐Jun Activation in Renal Cell Carcinoma

FosB transcription factor regulates COX-2 expression in colorectal cancer cells without affecting PGE2 expression

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