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Phospholipase A2 as targets for anti-cancer drugs
Authors:Cummings Brian S
Affiliation:Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA. bsc@rx.uga.edu
Abstract:Phospholipase A(2) (PLA(2)) are esterases that cleave glycerophospholipids to release fatty acids and lysophospholipids. Inhibition of PLA(2) alters cancer cell growth and death in vitro and PLA(2) expression is increased in breast, lung, and prostate cancers compared to control tissues. Thus, PLA(2) may be novel targets for chemotherapeutics. However, PLA(2) are a diverse family of enzymes, encompassing 19 members. The selectivity of these individual PLA(2) for phospholipids varies, as does their location within the cell, and tissue expression. Thus, their role in cancer may also vary. This review summarizes the expression of individual PLA(2) in cancers, focuses on the potential mechanisms by which these esterases mediate carcinogenesis, and suggests that select PLA(2) isoforms may be targets for anti-cancer drugs.
Keywords:BEL, bromoenol lactone   COX, cyclooxygenase   cPLA2, cytosolic phospholipase A2   CYPP450, cytochrome P450 monooxygneaes   EET, epoxyeicosatrienoic acid   HETE, hydroxyeicosatetraenoic acid   HPETE, hydroperoxyeicosatetraenoic acid   iPLA2, Ca2+-independent phospholipase A2   LOX, lipoxygenase   LTC4, leukotrienes   LysoPLD, lysophospholipid specific phospholipase D   NSAID, nonsteroidal anti-inflammatory drugs   PAF, platelet activating factor   PAF-HA, platelet activating factor-acetylhydrolase   PGE2, prostaglandins   PGI2, prostacyclins   PLA2, phospholipase A2   PPAR, peroxisomal proliferator activated receptor   sPLA2, secretory phospholipase A2   TXA2, thromboxanes
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