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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2018

Open Access 01-12-2018 | Research

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

Authors: Heng Zhou, Yu Liu, Chao Wang, Limei Liu, Huan Wang, Yaqian Zhang, Cong Long, Xiaoping Sun

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2018

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Abstract

Background

Epstein-Barr virus (EBV) is widely found in nasopharyngeal carcinoma (NPC) tissue and associated with poor prognosis of patients. EBV nuclear antigen 1 (EBNA1) is expressed in all NPC tumors and plays multiple biological roles in both virus and host cells. Triptolide is a natural product extracted from Tripterygium and shows anti-cancer activities. The goal of this work was to illustrate the anti-cancer effect of triptolide and elucidate a novel anti-apoptotic mechanism of EBNA1 in NPC cells encountered with triptolide.

Methods

In the present study, a CCK-8 assay was used to analyze the proliferation of NPC cells treated with triptolide in a dose- and time-dependent ways. Effects of triptolide on NPC cell cycle and apoptosis were investigated by flow cytometric analysis. EBNA1 expression in mRNA and protein levels was determined by quantitative real-time PCR and Western blot, respectively.

Results

Our results showed that triptolide effectively inhibited proliferation of NPC cells. Triptolide arrested NPC cell cycles in S phase and induced apoptosis through a caspase-9-dependent apoptosis pathway. Low-dose of triptolide reduced the half-life of EBNA1 and significantly decreased EBNA1 expression by promoting the process of proteasome-ubiquitin pathway. Over-expression of EBNA1, which was independent from EBV genome, effectively attenuated the apoptosis induced by triptolide. In addition, triptolide significantly inhibited proliferations of tumors induced by EBV-positive cells in vivo. Furthermore, EBNA1 were expressed in all NPC biopsies of Chinese patients.

Conclusions

In summary, our study provides the evidence that triptolide induces EBNA1 degradation and stimulates NPC apoptosis through mitochondria apoptotic pathway. In addition, EBNA1 assists NPC cells to resist triptolide-induced apoptosis through inhibiting caspase-9-dependent apoptotic pathway.
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Metadata
Title
Triptolide inhibits Epstein-Barr nuclear antigen 1 expression by increasing sensitivity of mitochondria apoptosis of nasopharyngeal carcinoma cells
Authors
Heng Zhou
Yu Liu
Chao Wang
Limei Liu
Huan Wang
Yaqian Zhang
Cong Long
Xiaoping Sun
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2018
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-018-0865-5

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