PMID- 20133051 OWN - NLM STAT- MEDLINE DCOM- 20100621 LR - 20220317 IS - 1872-7980 (Electronic) IS - 0304-3835 (Linking) VI - 293 IP - 1 DP - 2010 Jul 1 TI - Chrysin sensitizes tumor necrosis factor-alpha-induced apoptosis in human tumor cells via suppression of nuclear factor-kappaB. PG - 109-16 LID - 10.1016/j.canlet.2010.01.002 [doi] AB - 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. FAU - Li, Xin AU - Li X AD - Center for Disease Control and Prevention of Guangdong Province, 176 Xin Gang Road, Guangzhou, Guangdong Province 510300, PR China. FAU - Huang, Qing AU - Huang Q FAU - Ong, Choon-Nam AU - Ong CN FAU - Yang, Xing-Fen AU - Yang XF FAU - Shen, Han-Ming AU - Shen HM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100204 PL - Ireland TA - Cancer Lett JT - Cancer letters JID - 7600053 RN - 0 (CASP8 and FADD-Like Apoptosis Regulating Protein) RN - 0 (Flavonoids) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - 3CN01F5ZJ5 (chrysin) SB - IM MH - Apoptosis/*drug effects MH - CASP8 and FADD-Like Apoptosis Regulating Protein/antagonists & inhibitors/biosynthesis MH - Colorectal Neoplasms/*drug therapy MH - Down-Regulation/drug effects MH - Drug Synergism MH - Flavonoids/*pharmacology MH - HCT116 Cells MH - Hep G2 Cells MH - Humans MH - Immunoblotting MH - Liver Neoplasms/*drug therapy MH - NF-kappa B/antagonists & inhibitors/genetics/metabolism/*pharmacology MH - Nasopharyngeal Neoplasms/drug therapy MH - Neoplasms/*drug therapy/genetics/metabolism/pathology MH - Transfection MH - Tumor Necrosis Factor-alpha/*genetics/metabolism/pharmacology EDAT- 2010/02/06 06:00 MHDA- 2010/06/22 06:00 CRDT- 2010/02/06 06:00 PHST- 2009/12/01 00:00 [received] PHST- 2009/12/25 00:00 [revised] PHST- 2010/01/11 00:00 [accepted] PHST- 2010/02/06 06:00 [entrez] PHST- 2010/02/06 06:00 [pubmed] PHST- 2010/06/22 06:00 [medline] AID - S0304-3835(10)00015-7 [pii] AID - 10.1016/j.canlet.2010.01.002 [doi] PST - ppublish SO - Cancer Lett. 2010 Jul 1;293(1):109-16. doi: 10.1016/j.canlet.2010.01.002. Epub 2010 Feb 4.