Carcinogenesis Advance Access originally published online on May 5, 2005
Carcinogenesis 2005 26(9):1520-1526; doi:10.1093/carcin/bgi112
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Carcinogenesis vol.26 no.9 © Oxford University Press 2005; all rights reserved.
Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells
Laboratory of Cell Growth, Mail Code 151F, Department of Medicine, Northern California Institute for Research and Education and Veterans Affairs Medical Center, University of California-San Francisco, San Francisco, CA 94121, USA
* To whom correspondence should be addressed at: Laboratory of Cell Growth (151F), Veterans Affairs Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA. Tel: +1 415 750 6940; Fax: +1 415 750 6667; Email: millie.hughes-fulford{at}med.va.gov
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.
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