Berberine inhibits the proliferation of human nasopharyngeal carcinoma cells via an Epstein-Barr virus nuclear antigen 1-dependent mechanism

Abstract

Nasopharyngeal carcinoma (NPC) is a malignancy derived from the epithelial cells of the nasopharynx cavity, and is closely associated with Epstein-Barr virus (EBV) infection. In addition to NPC, EBV causes various human malignancies, such as gastric cancer, hematological tumors and lymphoepithelioma-like carcinomas. Epstein-Barr nuclear antigen 1 (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-8 (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 cell cycle 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 type Ⅱ 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 transcription 3 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 in vitro and in vivo.

The Hsp70 inhibitor 2-phenylethynesulfonamide inhibits replication and carcinogenicity of Epstein–Barr virus by inhibiting the molecular chaperone function of Hsp70

“…The plasmids pSG5 vector, pSG5-EBNA1, and pSG5-EBNA1ΔGA have been described previously 57 . The plasmid pEF-Flag-Hsp70 was constructed by inserting the Hsp70 sequence into the pEF vectors.…”

Isoimperatorin Induces Apoptosis of Nasopharyngeal Carcinoma Cells via the MAPK/ERK1/2 Signaling Pathway

“…As natural medicines, traditional Chinese medicines have the advantages of a high level of safety, specific curative effect, and ability to avoid developing drug resistant disease. Researchers have been studying the efficacy and mechanism of traditional Chinese medicines, such as berberine [15], baicalein [16,17], arctiin [18], nitidine chloride [19], and other monomers [20] and have found them to exert obvious anticancer effects. However, significant future research will be needed on related fields in order to better develop the use of traditional Chinese medicines.…”

Triptolide inhibits Epstein-Barr nuclear antigen 1 expression by increasing sensitivity of mitochondria apoptosis of nasopharyngeal carcinoma cells

“…As speculated, V-val EBNA1 had the anti-apoptosis effect similar to P-ala EBNA1. Our previous studies have reported that EBNA1 could assist malignance cells to inhibit berberine [ 34 ] or 17-DMAG [ 33 ]-induced cancer cells death. Here, both P-ala and V-val EBNA1 attenuated the killing effects of triptolide on EBV-positive and EBV-negative NPC cell lines, suggesting that targeting on EBNA1 is a substantial strategy of treating EBV-positive NPC.…”