title: Phospholipase A2 Isoforms as Novel Targets for Prevention and Treatment of Inflammatory and Oncologic Diseases.
abstract: Phospholipase A2s (PLA2s) are group of enzymes, which cleave phospholipids 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 PLA2s could be a better therapeutic target than the downstream enzymes cyclooxygense and lipoxygenase. Several isoforms of PLA2s exist; they are mainly divided into secretory PLA2s (sPLA2), cytosolic PLA2s (cPLA2), and calcium independent PLA2s (iPLA2), platelet activating factor- acyl hydrolase (PAF-AH), lysosomal PLA2 (LPLA2), adipose-specific PLA2 (Ad- PLA). Each isoform of PLA2s is different in its chemical structure and physiological functions. sPLA2s (Groups IIA, V and X) are well characterized as proinflammatory mediating enzymes but their role in cancer is controversial. Groups IVA, IVB and IVC cPLA2s 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 PLA2s 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 PLA2s 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.
authors.forename: Nagendra Sastry
authors.initials: NS
authors.lastname: Yarla
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, Miami, Florida 33169, USA.
authors.forename: Anupam
authors.initials: A
authors.lastname: Bishayee
authors.forename: Lakshmipathi
authors.initials: L
authors.lastname: Vadlakonda
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Chintala
authors.affiliation: Department of Biochemistry & Bioinformatics, GITAM Institute of Science, GITAM University, Rushikonda, Visakhapatnam - 530 045, India.
authors.forename: Govinda Rao
authors.initials: GR
authors.lastname: Duddukuri
authors.forename: Pallu
authors.initials: P
authors.lastname: Reddanna
authors.forename: Kaladhar S V G K
authors.initials: KS
authors.lastname: Dowluru
mesh_terms: D000818:Animals; D020134:Catalytic Domain / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000517:prevention & control* / Q000628:therapy; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000517:prevention & control* / Q000628:therapy; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D064801:Phospholipase A2 Inhibitors; D020033:Protein Isoforms; D054467:Phospholipases A2