Attenuation of breast tumor cell growth by conjugated linoleic acid via inhibition of 5-lipoxygenase activating protein.
Biochim Biophys Acta
; 1736(3): 244-50, 2005 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-16185917
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.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Ácidos Linoleicos Conjugados
/
Proliferação de Células
/
Proteínas de Membrana
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article