期刊
JOURNAL OF NUTRITION
卷 138, 期 11, 页码 2098-2105出版社
OXFORD UNIV PRESS
DOI: 10.3945/jn.108.090431
关键词
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资金
- Undergraduate Honors College, the University of Arizona, Tucson
- Graduate Training Program [T32 ES-07091-24]
- Arizona Biomedical Research Commission, Phoenix, AZ [0819]
One mechanism through which bioactive food components may exert anticancer effects is by reducing the expression of the proinflammatory gene cyclooxygenase-2 (COX-2), which has been regarded as a risk factor in tumor development. Rosmarinic acid (RA) is a phenolic derivative of caffeic acid present in rosemary (Rosmarinus officinalis). Previous research documented that RA may exert antiinflammatory effects. However, the mechanisms of action of RA on COX-2 expression have not been investigated. Here, we report that in color cancer HT-29 cells, RA (5, 10, and 20 mu mol/L) reduced the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced COX-2 promoter activity (P < 0.05) and protein levels (P < 0.05). In addition, the cotreatment with RA reduced (5 mu mol/L, P < 0.05, 10 and 20 mu mol/L, P < 0.01) TPA-induced transcription from a control activator protein-1 (AP-1) promoter-luciferase construct and repressed binding of the AP-1 factors c-Jun (10 mu mol/L, P < 0.01) and c-Fos (10 mu mol/L; P < 0.05) to COX-2 promoter oligonucleotides harboring a cAMP-response element (CRE). The anti-AP1 effects of RA were also examined in a nonmalignant breast epithelial cell line (MCF10A) in which RA antagonized the stimulatory effects of TPA on COX-2 protein expression (5 mu mol/L, P < 0.05; 10 and 20 mu mol/L, P < 0.01), the recruitment of c-Jun and c-Fos (10 mu mol/L; P < 0.01) to the COX-2/CRE oligonucleotides, and activation of the extracellular signal-regulated protein kinase-1/2 (ERK1/2) (10 mu mol/L, P < 0.01), a member of the mitogen-activated protein kinase pathway. Additionally, RA antagonized ERK1/2 activation in colon HT-29 and breast MCF-7 cancer cells (10 mu mo/L; P < 0,01). Thus, we propose that RA maybe an effective preventative agent against COX-2 activation by AP-1-inducing agents in both cancer and nonmalignant mammary epithelial cells. J. Nutr. 138: 2098-2105, 2008.
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