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 Romagnolo

Research output: Contribution to journalArticle

44 Citations (Scopus)

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
StatePublished - Feb 2006

Fingerprint

Conjugated Linoleic Acids
Transcription Factor AP-1
prostaglandin synthase
Cyclooxygenase 2
conjugated linoleic acid
breast neoplasms
Breast Neoplasms
response elements
Response Elements
Tetradecanoylphorbol Acetate
proteins
collagenase
transcription (genetics)
acetates
nuclear proteins
promoter regions
Nuclear Proteins
isomers
neoplasm cells
Electrophoretic Mobility Shift Assay

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

Conjugated linoleic acid attenuates cyclooxygenase-2 transcriptional activity via an anti-AP-1 mechanism in MCF-7 breast cancer cells. / Degner, Stephanie C.; Kemp, Michael Q.; Bowden, G. Tim; Romagnolo, Donato.

In: Journal of Nutrition, Vol. 136, No. 2, 02.2006, p. 421-427.

Research output: Contribution to journalArticle

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