Emodin Inhibits EBV Reactivation and Represses NPC Tumorigenesis

Abstract

Nasopharyngeal carcinoma (NPC) is a unique malignancy derived from the epithelium of the nasopharynx. Despite great advances in the development of radiotherapy and chemotherapy, relapse and metastasis in NPC patients remain major causes of mortality. Evidence accumulated over recent years indicates that Epstein-Barr virus (EBV) lytic replication plays an important role in the pathogenesis of NPC and inhibition of EBV reactivation is now being considered as a goal for the therapy of EBV-associated cancers. With this in mind, a panel of dietary compounds was screened and emodin was found to have potential anti-EBV activity. Through Western blotting, immunofluorescence, and flow cytometric analysis, we show that emodin inhibits the expression of EBV lytic proteins and blocks virion production in EBV- positive epithelial cell lines. In investigating the underlying mechanism, reporter assays indicated that emodin represses Zta promoter (Zp) and Rta promoter (Rp) activities, triggered by various inducers. Mapping of the Zp construct reveals that the SP1 binding region is important for emodin-triggered repression and emodin is shown to be able to inhibit SP1 expression, suggesting that it likely inhibits EBV reactivation by suppression of SP1 expression. Moreover, we also show that emodin inhibits the tumorigenic properties induced by repeated EBV reactivation, including micronucleus formation, cell proliferation, migration, and matrigel invasiveness. Emodin administration also represses the tumor growth in mice which is induced by EBV activation. Taken together, our results provide a potential chemopreventive agent in restricting EBV reactivation and NPC recurrence.

RETRACTED: Emodin Interferes With AKT1-Mediated DNA Damage and Decreases Resistance of Breast Cancer Cells to Doxorubicin

“…Emodin has been reported to have a wide spectrum of pharmacological applications, especially hepatoprotective, anti-inflammatory, antibacterial and anti-cancer effects. Evidence shows that Emodin has a tumor-suppressor activity in many cancers ( 33 , 34 ), especially the intrinsic insensitivity of cancer cells to drugs ( 34 ). Our in vivo and vitro assays showed that Emodin suppresses the cell growth and induces apoptosis in BC cells.…”

Molecular Mechanisms of Action of Emodin: As an Anti-Cardiovascular Disease Drug

“…Emodin (1, 3, 8-trihydroxy-6-methylanthraquinone) is a natural anthraquinone derivative, and is the main ingredient of many herbs including rhubarb, polygonum multiflorum , and polygonum cuspidatum ( Dong et al., 2016 ; Monisha et al., 2016 ). Pharmacological studies have shown that emodin, as a polyvalent molecule, has a variety of biological functions, such as anti-inflammatory ( Li X. et al., 2020 ; Xu et al., 2020 ), anti-bacterial ( Ji et al., 2020 ), anti-cancer ( Wu C. et al., 2019 ; Ma et al., 2020 ; Rossi et al., 2020 ) and inhibition of oxidative stress( Lee et al., 2020 ). Emodin has also been shown to have potent anti-cardiovascular activities in vitro and in vivo , including anti-inflammatory ( Wu et al., 2007 ), antioxidant damage ( Du and Ko, 2005 ), inhibition of myocardial cell fibrosis ( Evans et al., 2020 ) and other pharmacological effects.…”

Effect of Chinese Herbal Medicine Therapy on Overall and Cancer Related Mortality in Patients With Advanced Nasopharyngeal Carcinoma in Taiwan

“…XYQFT also contains natural compounds, including EGCG, apigenin, coumarin, genistein, and quercetin, which exhibit anti-NPC activities ( Ong et al, 2004 ; Han et al, 2010 ; Daker et al, 2012 ; Lin et al, 2014 ; Peng et al, 2018 ; Ho et al, 2019 ; Zhang et al, 2019 ). Furthermore, 1,3,8-trihydroxy-6-methylanthraquinone (emodin) from XYQFT inhibits EBV reactivation and suppresses NPC cell proliferation ( Ma et al, 2017 ; Wu et al, 2019 ). The 3-phenyl-2-propenal ( trans -cinnamaldehyde) inhibits NPC cells ( Daker et al, 2013 ).…”