br Introduction Nasopharyngeal carcinoma NPC

Introduction Nasopharyngeal carcinoma (NPC) is a head and neck epithelial malignancy with high prevalence in southern China, southeast Asia, and northern Africa [1,2]. NPC is caused by a combination of factors: infection with Epstein-Barr virus (EBV), environmental influences, and heredity [3]. Although the present therapies are multiple, NPC represents a significant disease burden due to the high rate of metastasis [4]. It has been reported that 74.5% of the patients have regional lymph node metastasis at the time of diagnosis, and 19.9% of the patients have distant metastasis, most often to the liver and lungs [[4], [5], [6]]. Better understanding of the underlying mechanisms of NPC may contribute to the development of effective targeted therapy of patients with this disease. The enhancer of zeste homolog 2 (EZH2) is one of the core submits of Polycomb Repressor Complex 2 (PRC2), which regulates the epigenetic gene silencing of target genes by promoting the methylation of histone H3 lysine 27 trimethylation (H3K27me3) [7]. Previous studies demonstrated that overexpression of EZH2 has been observed in a wide variety of cancers, including NPC [8,9]. The EZH2 erk pathway is often correlated with advanced stage, clinical aggressiveness and poor prognosis of cancers [8,9]. Therefore, it is supposed that targeting EZH2 may represent a promising strategy for cancer treatment [10]. Eudesmin (Fig. 1A) is a natural lignin that has been observed in various plants such as Apiaceae, Magnoliaceae, Ochnaceae and Rutaceae [11]. Pharmacological investigations have demonstrated that eudesmin possesses broad biological activities including antibacterial [12], antifungal [12], anticonvulsant [13], sedative [13] and vascular relaxation effects [11]. Recently, eudesmin was reported to exhibit antitumor effect on lung cancer [14], however, the effect of eudesmin on NPC has not been investigated. In the present study, we aimed to evaluate the role of eudesmin in NPC and explore the underlying mechanism.
Materials and methods
Results
Discussion Lignans are a group of diphenolic compounds that are widely distributed in various plants [16]. Although lignans are non-nutrient and non-caloric, they have attracted increasing attention due to their various biological properties, including antitumor, antiviral and antioxidant activities [16]. It has been reported that eudesmin possesses significant antitumor effects on lung cancer. The possible mechanism might be associated with the induction of mitochondria-mediated apoptosis [14]. Previous studies have demonstrated that some members of lignans have the ability to suppress NPC. Honokiol is a lignan that has been found to exhibit inhibitory effect on NPC, which is evidenced by the decreased proliferation, migration and invasion of NPC cell line CNE-1 cells [17]. However, the role of eudesmin in NPC has not been investigated. In the present study, we evaluated the effect of eudesmin on NPC cells. The results showed that eudesmin inhibited cell viability and induced apoptosis of NPC cells, suggesting that eudesmin might possess antitumor effect against NPC. Emerging evidence clearly suggests that EZH2 is overexpressed in NPC. Elevated EZH2 level is closely associated with an aggressive and poor prognostic phenotype, as well as positively correlated with microvessel density (MVD) in NPC tissues [9]. These findings suggest that high expression of EZH2 is associated with tumor angiogenesis in NPC. In vitro studies reveal that EZH2-silencing inhibits cell growth and migration in nasopharyngeal carcinoma cells. Besides, silencing of EZH2 has been found to block tubule formation of endothelial cells, indicating EZH2-silencing reduces cancer angiogenesis in vitro [9]. A previous study showed that high expression of EZH2 in NPC is closely associated with an aggressive and/or poor prognostic phenotype in patients with NPC. Further in vitro and in vivo experiments have denoted that knockdown of EZH2 by short hairpin RNA (shRNA) is sufficient to inhibit cell invasiveness/metastasis [18]. These findings suggest that EZH2 plays a critical role in the control of cell invasion and/or metastasis. Our results revealed that eudesmin suppressed the expression of EZH2 in NPC cells.