Oncology reports

Berberine inhibits the proliferation of human nasopharyngeal carcinoma cells via an Epstein-Barr virus nuclear antigenxa01-dependent mechanism.

PMID 28259949


Nasopharyngeal carcinomaxa0(NPC) is a malignancy derived from the epithelial cells of the nasopharynx cavity, and is closely associated with Epstein-Barr virusxa0(EBV) infection. In addition to NPC, EBV causes various human malignancies, such as gastric cancer, hematological tumors and lymphoepithelioma-like carcinomas. Epstein-Barr nuclear antigenxa01xa0(EBNA1) encoded by EBV is indispensable for replication, partition, transcription and maintenance of viral genomes. Berberine, a naturally occurring isoquinoline alkaloid, shows anti-inflammatory, anticholinergic, antioxidative, and anticancer activities. In the present study, the antitumor effect of berberine was studied. Cell Counting Kit-8xa0(CCK-8) assays were performed to demonstrate whether the proliferation of EBV-positive NPC cells was inhibited by berberine. Flow cytometric results revealed that berberine induced cellxa0cycle arrest and apoptosis. Quantitative-PCR and western blotting results indicated that berberine decreased the expression of EBNA1 at both the mRNA and protein levels in the EBV-positive NPC cells. The function of EBNA1 promoter Qp which is to drive EBNA1 transcription in typexa0Ⅱ latent infection was strongly suppressed by berberine. Overexpression of EBNA1 attenuated this inhibitory effect. Berberine also suppressed the activity of signal transducer and activator of transcriptionxa03 which is a new therapeutic target in a series of malignancies, including NPC. Viral titer experiments demonstrated that berberine decreased the production of virions in HONE1 and HK1-EBV cells. In a mouse xenograft model of NPC induced by HONE1 cells, berberine significantly inhibited tumor formation. Altogether, these results indicate that berberine decreases the expression of EBNA1 and exhibits an antitumor effect against NPC both inxa0vitro and inxa0vivo.

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Tris(2-pyridylmethyl)amine, 98%