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Journal of Lipid Research, Vol. 45, 1030-1039, June 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

Formation and antiproliferative effect of prostaglandin E₃ from eicosapentaenoic acid in human lung cancer cells

Peiying Yang^*, Diana Chan^*, Edward Felix^*, Carrie Cartwright^*, David G. Menter, Timothy Madden^*, Russell D. Klein, Susan M. Fischer and Robert A. Newman^1,*

^* Pharmaceutical Development Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77054
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Department of Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, TX 78957

¹ To whom correspondence should be addressed. e-mail: rnewman{at}mdanderson.org

We investigated the formation and pharmacology of prostaglandin E₃ (PGE₃) derived from fish oil eicosapentaenoic acid (EPA) in human lung cancer A549 cells. Exposure of A549 cells to EPA resulted in the rapid formation and export of PGE_3. The extracellular ratio of PGE₃ to PGE₂ increased from 0.08 in control cells to 0.8 in cells exposed to EPA within 48 h. Incubation of EPA with cloned ovine or human recombinant cyclooxygenase 2 (COX-2) resulted in 13- and 18-fold greater formation of PGE₃, respectively, than that produced by COX-1. Exposure of A549 cells to 1 µM PGE₃ inhibited cell proliferation by 37.1% (P < 0.05). Exposure of normal human bronchial epithelial (NHBE) cells to PGE₃, however, had no effect. When A549 cells were exposed to EPA (25 µM) or a combination of EPA and celecoxib (a selective COX-2 inhibitor), the inhibitory effect of EPA on the growth of A549 cells was reversed by the presence of celecoxib (at both 5 and 10 µM). This effect appears to be associated with a 50% reduction of PGE₃ formation in cells treated with a combination of EPA and celecoxib compared with cells exposed to EPA alone.

These data indicate that exposure of lung cancer cells to EPA results in a decrease in the COX-2-mediated formation of PGE₂, an increase in the level of PGE₃, and PGE₃-mediated inhibition of tumor cell proliferation.

Abbreviations: AA, arachidonic acid; BHT, butylated hydroxytoluene; calcein AM, acetoxymethyl ester of calcein; COX, cyclooxygenase; DAPI, 4',6-diamidino-2-phenylindole; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; LC/MS/MS, liquid chromatography/tandem mass spectrometry; NHBE, normal human bronchial epithelial; PGE₃, prostaglandin E₃

Supplementary key words -3 fatty acids • eicosanoid metabolism • cell proliferation • cyclooxygenase enzymes • malignant cells

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