Conjugated linoleic acid attenuates cyclooxygenase-2 transcriptional activity via an anti-AP-1 mechanism in MCF-7 breast cancer cells

Stephanie C. Degner, Michael Q. Kemp, G. Tim Bowden, Donato F. Romagnolo

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Overexpression of cyclooxygenase-2 (COX-2) is regarded as a causative factor in the onset of tumorigenesis of the breast. In this study, we investigated the effects of conjugated linoleic acid (CLA) on COX-2 transcription in MCF-7 breast cancer cells. Results of transient transfection studies revealed that treatment with a CLA mix or selected isomers (c9, t11-CLA; t10, c12-CLA) at concentrations ranging from 20 to 80 μmol/L, attenuated COX-2 transcription induced by the proinflammatory agent 12-O- tetradecanoylphorbol-13-acetate (TPA). In addition, the CLA mix inhibited TPA-induced activity of the collagenase-1 promoter. Using electrophoretic mobility shift assays, we found that the CLA mix reduced TPA-induced recruitment of nuclear proteins to a cAMP response element (CRE) in the COX-2 promoter and a consensus TPA-responsive element (TRE) in the collagenase-1 promoter. Both CRE and TRE are binding sites for activator protein-1 (AP-1). Binding studies revealed that the t10, c12-CLA isomer was more effective than the CLA mix or c9, t11-CLA in reducing binding of cJun to either the COX-2 CRE or collagenase-1 TRE, whereas linoleic acid increased binding to both elements. Overexpression of the AP-1 member, c-Jun, reversed the inhibitory effects of the CLA mix on COX-2 transcription, and restored binding of nuclear proteins to the CRE and TRE. Collectively, these results suggest that CLA represses AP-1-mediated activation of COX-2 transcription.

Original languageEnglish (US)
Pages (from-to)421-427
Number of pages7
JournalJournal of Nutrition
Volume136
Issue number2
DOIs
StatePublished - Feb 2006

Keywords

  • Activator protein-1
  • Breast cancer
  • Conjugated linoleic acid
  • Cyclooxygenase-2

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Fingerprint Dive into the research topics of 'Conjugated linoleic acid attenuates cyclooxygenase-2 transcriptional activity via an anti-AP-1 mechanism in MCF-7 breast cancer cells'. Together they form a unique fingerprint.

  • Cite this