Aryl hydrocarbon receptor-dependent apoptotic cell death induced by the flavonoid chrysin in human colorectal cancer cells. Issue 1 (1st January 2016)

• Record Type: Journal Article
• Authors: Ronnekleiv-Kelly, Sean M.; Nukaya, Manabu; Díaz-Díaz, Carol J.; Megna, Bryant W.; Carney, Patrick R.; Geiger, Peter G.; Kennedy, Gregory D.
• Is Part Of: Cancer letters. Volume 370:Issue 1(2016)
• Page Start: 91
• Page End: 99
• Publication Date: 2016-01-01
• Subjects: AHR aryl hydrocarbon receptor -- AP-1 activator protein 1 -- ARNT AHR nuclear translocator -- BAD Bcl-2-associated death promoter -- CYP cytochrome P450 -- DRE dioxin-responsive element -- ERK extracellular signal-regulated kinase -- FICZ 6-formylindolo (3, 2-b) carbazole -- IEGs immediate early genes -- JNK c-jun N-terminal kinase -- LTα lymphotoxin α -- MAPK mitogen-activated protein kinase -- NF-κB nuclear factor κ-light-chain enhancer of activated B cells -- PYCARD PYD and CARD domain containing -- rTdT recombinant terminal deoxynucleotidyl transferase -- siRNA small interfering RNA -- SRE serum response element -- SRF serum response factor -- TCDD 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin -- TCFs ternary and complex factors -- TNF tumor necrosis factor -- TNFR TNF receptor -- TUNEL terminal deoxynucleotidyl transferase-dUTP nick end labeling; Aryl hydrocarbon receptor -- Chrysin -- Apoptosis -- Colorectal cancer -- Tumor necrosis factor; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.10.014
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: The treatment of flavonoid chrysin showed a chemopreventive effect in human colorectal cancer cells via the apoptosis pathway. Up-regulation and activation of the tumor necrosis factor-mediated transcriptional pathway were involved in apoptosis. The aryl hydrocarbon receptor, a ligand-receptor for chrysin, is required for the induction of apoptosis. 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.