Soya isoflavones suppress phorbol 12-myristate 13-acetate-induced COX-2 expression in MCF-7 cells.
Epidemiological studies indicate that Asian women have a lower incidence of breast cancer compared with their counterparts in the West, and soya consumption has been suggested as a contributory factor. Clinical and animal studies have revealed that cyclooxygenase-2 (COX-2) expression is associated with a risk of breast cancer. In the present study, we investigated the effect of soya isoflavones on the expression of COX-2 in the breast cell line MCF-7. Genistein, daidzein and equol were found to inhibit COX-2 expression induced by phorbol 12-myristate 13-acetate (PMA). Similar findings were observed in the COX-2 protein analysis. In order to study transcriptional control, a fragment of the 5'-flanking region of the hCOX-2 gene was amplified and inserted into a firefly luciferase reporter plasmid. The reporter assay indicated that the transactivation of the hCOX-2 promoter was induced by PMA, and activity was inhibited with the co-administration of genistein, daidzein or equol. An activator protein-1 (AP-1)/cyclic AMP response element binding protein (CREB) binding site (-59/-53) was identified in hCOX-2 promoter, and this could be critical in PMA-induced COX-2 expression. Truncation reporter plasmids with (-70/-36) and without (-51/-36) AP-1/CREB were constructed for subsequent analysis. The results revealed that the hCOX-2 promoter transactivation suppressed by isoflavone could be dependent on AP-1/CREB binding. Nonetheless, this study illustrated that the soya isoflavones reduced COX-2 expression, which could be important in the post-initiation events of breast carcinogenesis.
Lau
Tak Yi
TY
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
Leung
Lai K
LK
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology; D002273:Carcinogens; D045744:Cell Line, Tumor; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D060754:Equol; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008565:Membrane Proteins / Q000032:analysis; D048789:Phytoestrogens / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D013025:Glycine max / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology
C007610:4',7-dihydroxy-3,4-dihydroisoflavone; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D052246:Cyclooxygenase 2 Inhibitors; D007529:Isoflavones; D008565:Membrane Proteins; D048789:Phytoestrogens; D010936:Plant Extracts; D060754:Equol; C016658:phorbolol myristate acetate; C004742:daidzein; D019833:Genistein; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013755:Tetradecanoylphorbol Acetate