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Carcinogenesis Advance Access originally published online on October 19, 2006
Carcinogenesis 2007 28(4):809-815; doi:10.1093/carcin/bgl183
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© The Author 2006. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Complementary actions of docosahexaenoic acid and genistein on COX-2, PGE2 and invasiveness in MDA-MB-231 breast cancer cells

Eva Horia and Bruce A. Watkins*

Center for Enhancing Foods to Protect Health, Lipid Chemistry and Molecular Biology Laboratory Purdue University, West Lafayette, IN 47907, USA

*To whom correspondence should be addressed. Tel: +1 765 494 5802; Fax: +1 765 494 7953; Email: baw{at}purdue.edu

N-3 polyunsaturated fatty acids (PUFA) and genistein have been associated with lowered cancer risk by reducing inflammatory prostanoids, cyclooxygenase-2 (COX-2) activity, and altering cell signaling. Few studies have investigated the effect of these compounds in combination on the molecular control of the COX-2 gene. In a series of experiments we examined a potential synchronous action of n-3 PUFA and genistein in down-regulating COX-2 expression to diminish prostaglandin E2 (PGE2) production in MDA-MB-231 human breast cancer cells. Cells were treated with genistein and various PUFA including arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PGE2 concentrations, expression of COX-2, and cell invasiveness were determined. The n-3 PUFA and genistein alone lowered PGE2 concentration, and genistein in combination with AA reversed the high level of this prostanoid in cell cultures enriched with AA. The degree of cell invasiveness was reversed by genistein in cell cultures treated with AA and further reduced in those given DHA. The n-3 PUFA, in contrast to AA, reduced COX-2 and NF{kappa}B expression. Genistein combined with AA reversed the effects of AA alone on the expression of COX-2 and NF{kappa}B. All three fatty acids increased the expression of PPAR{gamma} in the cells only when combined with genistein. Our results support the premise that DHA and genistein exert complementary actions whilst genistein is antagonistic to AA for controlling PGE2 production as well as invasiveness of MDA-MB-231 cells in culture by modulating the level of NF{kappa}B expression.

Abbreviations: AA, arachidonic acid; COX, cyclooxygenase; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; IL, interleukin; LA, linoleic acid; NF{kappa}B, nuclear factor kappa B; PGE2, prostaglandin E2; PPAR, peroxisome proliferator activated receptor; PPRE, peroxisome proliferator receptor element; LC-PUFA, long-chain polyunsaturated fatty acids; Q-PCR, quantitative polymerase chain reaction; TNF{alpha}, tumor necrosis factor-{alpha}.

Received March 17, 2006; revised August 20, 2006; accepted September 11, 2006.


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