title: Chrysin promotes tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induced apoptosis in human cancer cell lines.
abstract: Chrysin exists widely in plants, honey and propolis. The anti-cancer property of chrysin has been demonstrated though the molecular mechanism is not clear. In this study, we found that pre-treatment with chrysin could promote the cell death induced by TRAIL according to the morphological changes and appearance of sub-G1 peak in four human cancer cell lines. In HCT-116 cells, the results of flow cytometry analysis showed that the percentage of sub-G1 reached (38.89 ± 3.78) % when pre-treatment of chrysin was used at 40 μM, but that was only (2.53 ± 0.10) % in the untreated group and (13.22 ± 0.20) % in TRAIL alone group. The differences between the combination and the untreated or TRAIL alone group were all significant (P<0.05) and dose-dependent effect was obvious. Similar results were obtained in CNE1 cells. In the search of molecular mechanisms, we found that pre-treatment with chrysin could increase TRAIL-induced degradation of caspase 3, caspase 8, PARP proteins. Z-VAD-fmk, which is a pan-caspase inhibitor, could inhibit the apoptosis enhanced by the combination of chrysin and TRAIL. All data indicate that chrysin can enhance the apoptosis induced by TRAIL, and the apoptosis is caspase-dependent and related to the activation of caspase 8.
authors.affiliation: Center for Disease Control and Prevention of Guangdong Province, 176 Xin Gang West Road, Guangzhou, Guangdong Province 510300, PR China. lixinsm@gmail.com
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Wang
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Huang
authors.forename: Xi-Kun
authors.initials: XK
authors.lastname: Xiong
authors.forename: Mei-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Choon-Nam
authors.initials: CN
authors.lastname: Ong
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Shen
authors.forename: Xing-Fen
authors.initials: XF
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004338:Drug Combinations; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005419:Flavonoids / Q000494:pharmacology*; D045325:HCT116 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D005419:Flavonoids; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C043561:chrysin; D053148:Caspase 3; D053181:Caspase 8