Inhibition of epstein‐barr virus reactivation in nasopharyngeal carcinoma cells by dietary sulforaphane

Abstract

Epstein-Barr virus (EBV) has been associated with several human malignancies including nasopharyngeal carcinoma (NPC). Reactivation of latent EBV has been considered to contribute to the carcinogenesis of NPC. Blocking the EBV lytic cycle has been shown effective in the treatment of EBV-associated diseases. We have searched for natural dietary compounds inhibiting EBV reactivation in NPC cells. Among them, sulforaphane (SFN) was found to be effective in the inhibition of EBV reactivation in latent EBV-positive NPC cells, NA and HA. SFN is a histone deacetylase (HDAC) inhibitor and has been recognized as an antioxidant and antitumor compound for chemoprevention. However, its antiviral effect is less well elucidated. In this study, after determination of the cytotoxicity of SFN on various epithelial cells, we showed that SFN treatment inhibits EBV reactivation, rather than induction, by detection of EBV lytic gene expression in EBV-positive NPC cells. We also determined that the number of cells supporting the EBV lytic cycle is decreased using immunofluorescence and flow cytometric analysis. Moreover, we have found that this inhibitory effect decreases virus production. To elucidate the inhibitory mechanism of SFN on the EBV lytic cycle, luciferase reporter assays were carried out on the Zta and Rta promoters. The results show that SFN inhibits transactivation activity of the EBV immediate-early gene Rta but not Zta. Together, our results suggest that SFN has the capability to inhibit EBV lytic cycle and the potential to be taken as a dietary compound for prevention of EBV reactivation.

Luteolin inhibits Epstein-Barr virus lytic reactivation by repressing the promoter activities of immediate-early genes

“…The construction of the Zp and Rp reporter plasmids has been described in previous reports (Huang et al, 2010;Tsai et al, 2011;Wu et al, 2013). In addition, the Sp1-luc reporter containing the Sp1 binding site was purchased from a commercial company (Invitrogen).…”

“…maribavir, has been found to block EBV transcription and replication (Wang et al, 2009). (iii) In addition to chemicals, dietary ingredients such as retinoic acid, epigallocatechin gallate (EGCG), curcumin and sulforaphane (SFN) also have been suggested to have the potential to inhibit the EBV lytic cycle (Chang et al, 2003;Hergenhahn et al, 2002;Sista et al, 1993;Wu et al, 2013). Regarding clinical application, dietary compounds are more attractive for inhibition of the EBV lytic cycle because of their low cost and convenience.…”

Inhibition of Epstein-Barr virus reactivation by the flavonoid apigenin

“…Western blotting has been described in our previous report [23]. Briefly, the samples were subjected to SDS-PAGE and then transferred to Hybond-C membranes (Amersham Biosciences Ltd.).…”

“…(iii) Dietary ingredients, e.g. retinoic acid, epigallocatechin gallate, curcumin and sulforaphane, also have been suggested to have the potential to inhibit the EBV lytic cycle [20–23]. Regarding clinical application, dietary compounds are attractive for the inhibition of EBV reactivation because of their safety and convenience.…”

Brassica oleracea (Italica Group)

“…Sulforaphane was found to inhibit Epstein-Barr virus (EBV) reactivation in nasopharyngeal carcinoma cells, thereby decreasing virus production (Wu et al 2012 ). It was found that sulforaphane inhibited transactivation activity of the EBV immediate-early gene Rta but not Zta and had the capability to inhibit EBV lytic cycle.…”