Phospholipase A<inf>2</inf> isoforms as novel targets for prevention and treatment of inflammatory and oncologic diseases

Abstract

Phospholipase A2 s (PLA2 s) are group of enzymes, which cleave phosphol-ipids specifically at sn-2 position to liberate free fatty acid, mostly arachidonic acid (AA) and lysophospholipids (LPLs). Inhibition of PLA2 prevents the liberation of AA and LPLs. Hence, researchers have been considering PLA2 s could be a better therapeutic target than the downstream enzymes cyclooxygense and lipoxygenase. Several isoforms of PLA2 s exist; they are mainly divided into secretory PLA2 s (sPLA2), cytosolic PLA2 s (cPLA2), and calcium independent PLA2 s (iPLA2), platelet activating fac-tor-acyl hydrolase (PAF-AH), lysosomal PLA2 (LPLA2), adipose-specific PLA2 (Ad-PLA). Each isoform of PLA2 s is different in its chemical structure and physiological functions. sPLA2 s (Groups IIA, V and X) are well characterized as proinflammatory mediating enzymes but their role in cancer is controversial. Groups IVA, IVB and IVC cPLA2 s are present in humans but only Group IVA cPLA2 plays key role in pathophysiology of various cancers and inflammation. The role of iPLA2 in inflammation and cancer is limited. Lipoprotein associated PLA2 (Group VIIA PLA2), a PAF-AH isoform, has key role in atherosclerosis. Several isoform specific PLA2 inhibitors have been developed and some of the PLA2 s inhibitors are currently under clinical trials for various inflammatory and oncologic diseases. This review focuses on the recent experimental evidences to support the notion that PLA2 s are causally implicated in the pathobiology of cancer and inflammatory related disorders and discuss the potential utility of isoform specific PLA2 inhibitors as preventive and/or therapeutic agents.