Involvement of Nuclear Factor κB (NF-κB) in the Downregulation of Cyclooxygenase-2 (COX-2) by Genistein in Gastric Cancer Cells

Genistein induces growth inhibition in various human cancer cell lines but its mechanism of action remains unknown. This study determined whether the effect of genistein is mediated via suppression of cyclo-oxygenase (COX)-2 protein, and elucidated the mechanism of action of this effect in the human gastric cancer cell line BGC-823. Genistein treatment inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner; Western blotting analysis indicated a significant dose-dependent decrease in COX-2 protein levels. Genistein treatment exerted a significant inhibitory effect on activation of the transcription factor nuclear factor kappa B (NF-kappa B). Additionally, the NF-kappa B inhibitor pyrrolidine dithiocarbamate caused a reduction in COX-2 protein levels and NF-kappa B activation, similar to the effect of genistein. Suppression of COX-2 protein may be important for the antiproliferative and proapoptotic effects of genistein in BGC-823 cells, and these effects may be partly mediated through the NF-kappa B pathway.