Carcinogenesis Advance Access published online on May 5, 2005
Carcinogenesis, doi:10.1093/carcin/bgi112
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1 Department of Medicine, University of California-San Francisco, San Francisco CA; Northern California Institute for Research and Education, Veterans Affairs Medical Center, San Francisco CA; Laboratory of Cell Growth (151F), Veterans Affairs Medical Center, San Francisco CA
* To whom correspondence should be addressed. For the past sixty years, dietary intake of essential fatty acids has increased. Moreover, the
Received February 21, 2005
Revised April 14, 2005
Accepted April 26, 2005
CANCER BIOLOGY
Arachidonic acid, an Omega-6 fatty acid, induces cytoplasmic phospholipase A2 in prostate carcinoma cells
Millie Hughes-Fulford, E-mail: milliehf{at}aol.com; millie.hughes-fulford@med.va.gov
Abstract 
-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 forty-eight hours after AA addition. We have analyzed initial uptake using nile red fluorescence and we found that the albumin conjugated arachidonic acid (AA) is endocytosed into the cells followed by 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 upreglation is dependent upon downstream synthesis of PGE2. The up-regulation of cox-2 and cPLA2 was inhibited by flurbiprofen, a cyclooxygenase 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 c-PLA2 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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