Interference of Fisetin with Nuclear Factor-κB Signal Transduction Activated by EBV Latent Membrane

The flavonoid fisetin (3, 3, 4, 7-tetrahydroxyflavone) is the main component of lacquer and is found in strawberries, apples, and grapes. The lacquer, lac tree extract, has been used as Chinese medicine in Asia for thousands of years. Several recent studies have demonstrated that the flavonoid has anticancer effects against several cancer types. Our preliminary data have indicated that fisetin induces cell cycle arrest and causes apoptosis in hepatocellular carcinoma cells (Li et al., 2010; 2011). However, the effect of fisetin on nasopharyngeal carcinoma (NPC) has not been studied extensively. Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has been known to have oncogenic properties during latent infection in nasopharyngeal carcinoma (NPC) . In human epithelial cells, LMP1 alters many functional properties that are involved in tumor progression and invasions (Kim et al., 2000; Adham et al., 2012; Bambang et al., 2010). Activation of different signal transduction pathways mediates various downstream pathological effects of LMP1 expression, including cell proliferation, anti-apoptosis and metastasis (Eliopoulos et al, 2001; Guo et al., 2012). NF-κB participates in the induction of cellular genes encoding apoptosis molecules (Xu et al., 2012; Yang et al., 2012). In NPC cells, NF-κB plays a critical role in LMP1