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

Autor: Peiying Yang, Diana Chan, Edward Felix, Carrie Cartwright, David G. Menter, Timothy Madden, Russell D. Klein, Susan M. Fischer, Robert A. Newman
Jazyk: angličtina
Rok vydání: 2004
Předmět:
Zdroj: Journal of Lipid Research, Vol 45, Iss 6, Pp 1030-1039 (2004)
Druh dokumentu: article
ISSN: 0022-2275
DOI: 10.1194/jlr.M300455-JLR200
Popis: 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 PGE3. 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.
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