Aryl hydrocarbon receptor-dependent apoptotic cell death induced by the flavonoid chrysin in human colorectal cancer cells

作者：Ronnekleiv Kelly Sean M; Nukaya Manabu; Diaz Diaz Carol J; Megna Bryant W; Carney Patrick R; Geiger Peter G; Kennedy Gregory D^*

来源：Cancer Letters, 2016, 370(1): 91-99.

DOI：10.1016/j.canlet.2015.10,014

• Aryl hydrocarbon receptor
• Chrysin
• Apoptosis
• Colorectal cancer
• Tumor necrosis factor

The polyphenolic flavone chrysin has been evaluated as a natural chemopreventive agent due to its anticancer 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) alpha and beta 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 Tnf alpha and beta 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 Tnf alpha and beta gene expression in human colorectal cancer cells.

• 出版日期2016