Attenuation of breast tumor cell growth by conjugated linoleic acid via inhibition of 5-lipoxygenase activating protein

Jung Hyun Kim, Neil Hubbard, Vincent Ziboh, Kent L Erickson

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Conjugated linoleic acid (CLA) consists of a group of linoleic acid geometric isomers that have been shown to reduce tumor growth and metastasis in animal models of breast, prostate and colon cancer. To delineate a possible mechanism of action for CLA, we have recently shown that the 5-lipoxygenase product, 5-hydroxyeicosatetraenoic acid (5-HETE), could play a role in CLA alteration of mammary tumorigenesis. In this study, we determined how CLA could modulate 5-lipoxygenase activity. The t10, c12-CLA isomer reduced production of 5-HETE but not 12- and 15-HETE in MDA-MB-231 human breast tumor cells. That isomer and the c9, t11-CLA isomer decreased 5-HETE production by competition with the lipoxygenase substrate, arachidonic acid (AA). Interestingly, t10, c12-CLA reduced the expression of five-lipoxygenase activating protein (FLAP) but not the 5-lipoxygenase enzyme. Over-expression of FLAP abrogated t10, c12-CLA-reduced viability of MDA-MB-231 cells. These data suggest that the reduction of 5-HETE by t10, c12-CLA was due to competition with AA and the reduction of FLAP expression.

Original languageEnglish (US)
Pages (from-to)244-250
Number of pages7
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1736
Issue number3
DOIs
StatePublished - Oct 1 2005

Keywords

  • 5-hydroxyeicosatetraenoic acid
  • 5-lipoxygenase
  • 5-lipoxygenase-activating protein
  • Conjugated linoleic acid

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Biophysics

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