Effect of arachidonic acid and its producing enzyme phospholipase A2α on key oncogenic pathways in prostate cancer

The dietary arachidonic acid (AA) is stored at the sn-2 position in the glycerolphospholipid of cell membrane. AA is released via the cleavage by phospholipase A2 in response to stimuli such as cytokines, growth factors and hormones. The freed AA is metabolised typically by cyclooxygenase and lipoxygenase enzymes to form eicosanoids. Of all the phospholipase A2 that catalyse the hydrolysis of fatty acid at sn-2 bond of glycerophospholipids, cytosolic phospholipase A2α (cPLA2α) is preferentially targeting AA-containing phospholipids. Hence, cPLA2α action represents the key step for AA release and eicosanoid synthesis. Stimulation of cells with agents that mobilise intracellular calcium and/or promote the phosphorylation of cPLA2α leads to increased AA release and eicosanoid production.