The dietary flavonoid apigenin blocks phorbol 12-myristate 13-acetate-induced COX-2 transcriptional activity in breast cell lines.

Cyclooxygenase (COX)-2 is the inducible isozyme catalyzing the conversion of arachidonic acid to prostanoids. Its expression has been linked to the process of carcinogenesis, including tumorigenesis of the breast. Apigenin (APG) is a flavone commonly found in fruit and vegetables, and is shown to be a potential modulator in inflammatory diseases. This study examined the potential suppressive effect of the flavone on phorbol ester-induced COX-2 expression in the breast cell lines MCF-10A and MCF-7. Real-time PCR and/or Western blotting indicated that APG in micromolar range significantly inhibited phorbol 12-myristate 13-acetate (PMA)-induced COX-2 expression in these breast cells. APG treatment reduced the amount of phospho-mitogen-activated protein kinase (MAPK) ERK-1/2, but it did not alter the activity of PKC. Activated ERKs might trigger the transactivation of AP-1 or CRE, which can be located at COX-2 promoter region (-72/-53). Reporter gene assay as well as electrophoretic mobility shift assays (EMSA) illustrated that APG inhibited transcription factor binding at this region in a dose-dependent manner. This study showed that APG down-regulated PMA-induced COX-2 expression in breast cells without affecting PKC activity. These findings could provide a scientific basis for developing APG nutraceutical against breast carcinogenesis.