Journal Article

Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A<sub>2</sub> in prostate carcinoma cells

Millie Hughes-Fulford, Raymond R. Tjandrawinata, Chai-Fei Li and Sina Sayyah

in Carcinogenesis

Volume 26, issue 9, pages 1520-1526
Published in print September 2005 | ISSN: 0143-3334
Published online May 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi112
Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells

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For the past 60 years, dietary intake of essential fatty acids has increased. Moreover, the omega-6 fatty acids have recently been found to play an important role in regulation of gene expression. Proliferation of human prostate cells was significantly increased 48 h after arachidonic acid (AA) addition. We have analyzed initial uptake using nile red fluorescence and we found that the albumin conjugated AA is endocytosed into the cells followed by the induction of RNA within minutes, protein and PGE2 synthesis within hours. Here we describe that AA induces expression of cytosolic phospholipase A2 (cPLA2) in a dose-dependent manner and that this upregulation is dependent upon downstream synthesis of PGE2. The upregulation of cox-2 and cPLA2 was inhibited by flurbiprofen, a cyclooxygenase (COX) inhibitor, making this a second feed-forward enzyme in the eicosanoid pathway. Cox-2 specific inhibitors are known to inhibit colon and prostate cancer growth in humans; however, recent findings show that some of these have cardiovascular complications. Since cPLA2 is upstream in the eicosanoid pathway, it may be a good alternative for a pharmaceautical target for the treatment of cancer.

Keywords: ω-6 FAs, omega-6 fatty acids; AA, arachidonic acid; COX, cyclooxygenase; EIA, Enzyme immunoassay; LA, linoleic acid; LDLr, low-density lipoprotein receptor; LT, leukotrienes; NSAIDs, nonsteroidal anti-inflammatory drugs; PG, prostaglandins; TX, thromboxanes

Journal Article.  5481 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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