HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M400474-JLR200v1 46/6/1278    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Denkins, Y. Articles by Marchetti, D. Search for Related Content PubMed PubMed Citation Articles by Denkins, Y. Articles by Marchetti, D. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 46, 1278-1284, June 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Role of -3 polyunsaturated fatty acids on cyclooxygenase-2 metabolism in brain-metastatic melanoma

Yvonne Denkins¹, Doty Kempf, Melissa Ferniz, Shilpa Nileshwar and Dario Marchetti

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803

Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M400474-JLR200

¹ To whom correspondence should be addressed. e-mail: ydenkins{at}vetmed.lsu.edu

Cyclooxygenase-2 (COX-2) is important in the progression of epithelial tumors. Evidence indicates that -6 PUFAs such as arachidonic acid (AA) promote the growth of tumor cells; however, -3 fatty acids [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] inhibit tumor cell proliferation. We investigated the effects of -3 PUFA on the expression and function of COX-2 in 70W, a human melanoma cell line that metastasizes to the brain in nude mice. We show that 1) tumor necrosis factor- upregulates the expression of both COX-2 mRNA and prostaglandin E₂ (PGE₂) production, and 2) -3 and -6 PUFA regulate COX-2 mRNA expression and PGE₂ production. AA increased COX-2 mRNA expression and prostaglandin production in -6-stimulated 70W cells. Conversely, COX-2 mRNA expression decreased in cells incubated with EPA or DHA. AA increased Matrigel^TM invasion 2.4-fold, whereas EPA or DHA did not. Additionally, PGE₂ increased in vitro invasion 2.5-fold, whereas exposure to PGE₃ significantly decreased invasion. Our results demonstrate that incubation of 70W cells with either AA or PGE₂ increased invasiveness, whereas incubation with EPA or DHA downregulated both COX-2 mRNA and protein expression, with a subsequent decrease in Matrigel^TM invasion.

Taken together, these results indicate that -3 PUFA regulate COX-2-mediated invasion in brain-metastatic melanoma.

Abbreviations: AA, arachidonic acid; COX-2, cyclooxygenase-2; DHA, docosahexaenoic acid; EIA, enzyme immunoassay; EPA, eicosapentaenoic acid; NSAID, nonsteroidal anti-inflammatory drugs; NS-398, N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; PGE₂, prostaglandin E₂; TNF-, tumor necrosis factor-

Supplementary key words arachidonic acid • brain melanoma • cancer • docosahexaenoic acid • eicosapentaenoic acid • polyunsaturated fatty acids • prostaglandin E₂ • prostaglandin E₃ • -6 polyunsaturated fatty acids

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				U. N Das Is depression a low-grade systemic inflammatory condition? Am. J. Clinical Nutrition, June 1, 2007; 85(6): 1665 - 1666. [Full Text] [PDF]

				B. N. Ames Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage PNAS, November 21, 2006; 103(47): 17589 - 17594. [Abstract] [Full Text] [PDF]

				R. J Deckelbaum, T. S Worgall, and T. Seo n-3 Fatty acids and gene expression Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1520 - 1525S. [Abstract] [Full Text] [PDF]