Chrysin sensitizes tumor necrosis factor-alpha-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 (TNFalpha)-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 TNFalpha-mediated nuclear transcription factor-kappaB (NF-kappaB) activation. Pretreatment with chrysin inhibited TNFalpha-induced degradation of Inhibitor of kappaB (IkappaB) protein and subsequent nuclear translocation of p65. As a result, chrysin suppressed the expression of NF-kappaB-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 TNFalpha. Data from this study thus reveal a novel function of chrysin and enhance the value of chrysin as an anti-cancer agent.
Li
Xin
X
Center for Disease Control and Prevention of Guangdong Province, 176 Xin Gang Road, Guangzhou, Guangdong Province 510300, PR China.
Huang
Qing
Q
Ong
Choon-Nam
CN
Yang
Xing-Fen
XF
Shen
Han-Ming
HM
D017209:Apoptosis / Q000187:drug effects*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D015151:Immunoblotting; D008113:Liver Neoplasms / Q000188:drug therapy*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D005419:Flavonoids; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C043561:chrysin