title: The dietary flavonoid apigenin blocks phorbol 12-myristate 13-acetate-induced COX-2 transcriptional activity in breast cell lines.
abstract: 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.
authors.affiliation: Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Grace Tak
authors.initials: GT
authors.lastname: Yi Lau
authors.forename: Lai K
authors.initials: LK
authors.lastname: Leung
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology*; D053148:Caspase 3 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015232:Dinoprostone / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D016195:G2 Phase / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D047310:Apigenin; D008156:Luciferases; D051546:Cyclooxygenase 2; D011494:Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D015232:Dinoprostone; D013755:Tetradecanoylphorbol Acetate