The Dietary Flavonol Kaempferol Inhibits Epstein–Barr Virus Reactivation in Nasopharyngeal Carcinoma Cells
Chung-Chun Wu, Ting-Ying Lee, Yu-Jhen Cheng, Der‐Yang Cho, Jen‐Yang Chen
Abstract
Kaempferol (KP, 3,4',5,7-tetrahydroxyflavone), a dietary flavonol, has anti-cancer, antioxidant, anti-inflammatory, antimicrobial, and antimutagenic functions. However, it is unknown whether kaempferol possesses anti-Epstein-Barr virus (EBV) activity. Previously, we demonstrated that inhibition of EBV reactivation represses nasopharyngeal carcinoma (NPC) tumourigenesis, suggesting the importance of identifying EBV inhibitors. In this study, Western blotting, immunofluorescence staining, and virion detection showed that kaempferol repressed EBV lytic gene protein expression and subsequent virion production. Specifically, kaempferol was found to inhibit the promoter activities of Zta and Rta (Zp and Rp) under various conditions. A survey of the mutated Zp constructs revealed that Sp1 binding regions are critical for kaempferol inhibition. Kaempferol treatment repressed Sp1 expression and decreased the activity of the Sp1 promoter, suggesting that Sp1 expression was inhibited. In conclusion, kaempferol efficiently inhibits EBV reactivation and provides a novel choice for anti-EBV therapy and cancer prevention.