Arachidonic acid, an omega-6 fatty acid, induces cytoplasmic phospholipase A₂ in prostate carcinoma cells

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.