Genistein inhibits phorbol ester-induced NF-κB transcriptional activity and COX-2 expression by blocking the phosphorylation of p65/RelA in human mammary epithelial cells.

摘要: Genistein, an isoflavone present in soy products, has chemopreventive effects on mammary carcinogenesis. In the study, we have investigated of genistein phorbol ester-induced expression cyclooxygenase-2 (COX-2) that plays important role pathophysiology inflammation-associated Pretreatment cultured human breast epithelial (MCF10A) cells with reduced COX-2 induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). There are multiple lines evidence supporting induction is regulated eukaryotic transcription factor NF-κB. Genistein failed to inhibit TPA-induced nuclear translocation and DNA binding NF-κB as well degradation IκB. However, abrogated transcriptional activity determined luciferase reporter gene assay. inhibited phosphorylation p65 subunit its interaction cAMP regulatory element-binding protein-binding protein (CBP)/p300 TATA-binding (TBP). was abolished pharmacological inhibition extracellular signal-regulated kinase (ERK). Likewise, pharmacologic or dominant negative mutation ERK suppressed p65. The above findings, taken together, suggest inhibits MCF10A blocking ERK-mediated subsequent CBP TBP.