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Soya isoflavones suppress phorbol 12-myristate 13-acetate-induced COX-2 expression in MCF-7 cells

Published online by Cambridge University Press:  08 March 2007

Tak Yi Lau  and
Lai K. Leung
Tak Yi Lau
Affiliation:
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
Lai K. Leung*
Affiliation:
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong
*
*Corresponding author: Dr Lai K. Leung, fax +852 26037732, email laikleung@yahoo.com
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Abstract

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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.

Keywords

GenisteinDaidzeinEquolCOX-2Breast cancer cells
Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 1 , January 2006 , pp. 169 - 176
Copyright
Copyright © The Nutrition Society 2006

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