title: Aryl hydrocarbon receptor-dependent apoptotic cell death induced by the flavonoid chrysin in human colorectal cancer cells.
abstract: The polyphenolic flavone chrysin has been evaluated as a natural chemopreventive agent due to its anti-cancer effects in a variety of cancer cell lines. However, the mechanism of the chemopreventive effect has been not well established, especially in human colorectal cancer cells. We evaluated the chemopreventive effect of chrysin in three different human colorectal cancer cell lines. We found that chrysin treatment consequently reduced cell viability via induction of apoptosis. We identified that the involvement of up-regulation of pro-apoptotic cytokines tumor necrosis factor (Tnf) α and β genes and consequent activation of the TNF-mediated transcriptional pathway in chrysin-induced apoptosis. Using our generated AHR siRNA expressing colorectal cancer cells, we demonstrated that the chrysin-induced up-regulation of Tnfα and β gene expression was dependent on the aryl hydrocarbon receptor (AHR), which is a ligand-receptor for chrysin. Subsequently, we found that the AHR siRNA expressing colorectal cancer cells were resistant to chrysin-induced apoptosis. Therefore, we concluded that AHR is required for the chrysin-induced apoptosis and the up-regulation of Tnfα and β gene expression in human colorectal cancer cells.
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G4/701A CSC, Madison, WI 53792, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Ronnekleiv-Kelly
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G4/701A CSC, Madison, WI 53792, USA.
authors.forename: Manabu
authors.initials: M
authors.lastname: Nukaya
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G4/701A CSC, Madison, WI 53792, USA.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Díaz-Díaz
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G4/701A CSC, Madison, WI 53792, USA.
authors.forename: Bryant W
authors.initials: BW
authors.lastname: Megna
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G4/701A CSC, Madison, WI 53792, USA.
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Carney
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G4/701A CSC, Madison, WI 53792, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Geiger
authors.affiliation: Department of Surgery, School of Medicine and Public Health, University of Wisconsin, 600 Highland Avenue, G4/701A CSC, Madison, WI 53792, USA. Electronic address: kennedyg@surgery.wisc.edu.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kennedy
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D005419:Flavonoids / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008233:Lymphotoxin-alpha / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D027602:Serum Response Element / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology
chemical_list: D005419:Flavonoids; D008233:Lymphotoxin-alpha; D018336:Receptors, Aryl Hydrocarbon; D014409:Tumor Necrosis Factor-alpha; C043561:chrysin; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2
keywords: Apoptosis; Aryl hydrocarbon receptor; Chrysin; Colorectal cancer; Tumor necrosis factor