Chrysin sensitizes tumor necrosis factor-α-induced apoptosis in human tumor cells via suppression of nuclear factor-kappaB

Chrysin (5,7-dihydroxyflavone) is a natural flavonoid commonly found in many plants. The anti-cancer property of chrysin has been demonstrated although the molecular mechanisms remain to be further elucidated. In the present study, we found that, pretreatment with chrysin greatly sensitized various human cancer cells to tumor necrosis factor-alpha (TNFα)-induced apoptosis. In the search of the molecular mechanisms responsible for the sensitization effect of chrysin, we discovered that such sensitization is closely associated with the inhibitory effect of chrysin on TNFα-mediated nuclear transcription factor-kappaB (NF-κB) activation. Pretreatment with chrysin inhibited TNFα-induced degradation of Inhibitor of kappaB (IκB) protein and subsequent nuclear translocation of p65. As a result, chrysin suppressed the expression of NF-κB-targeted anti-apoptotic gene, c-FLIP-L. The role of c-FLIP-L was further confirmed by its ectopic expression, which significantly protected cell death induced by combined treatment with chrysin and TNFα. Data from this study thus reveal a novel function of chrysin and enhance the value of chrysin as an anti-cancer agent.