title: Group IIa sPLA2 inhibition attenuates NF-κB activity and promotes apoptosis of lung cancer cells.
abstract: OBJECTIVE
  Group IIa secretory phospholipase A2 (sPLA2 IIa) has been implicated in the regulation of metastasis of non-small cell lung cancer (NSCLC) and the present study investigates its contribution to lung cancer growth and progression. PLA2s initiate signaling in several pathways that mediate cell survival including phosphatidylinositol 3-kinase-AKT (PI3K-AKT), p38 mitogen-activated protein kinase (p38 MAPK), extracellular-signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).
  
  
  METHODS
  Human NSCLC cell lines (A549 and NCI-H358) were treated with a specific sPLA2 IIa inhibitor. Cells were assayed for apoptosis, viability, proliferation and changes in cell morphology. Effects on AKT, p38 MAPK, ERK1/2 and NF-κB signaling pathways were investigated.
  
  
  RESULTS
  sPLA2 IIa inhibition reduced proliferation and increased apoptosis. NF-κB activity was attenuated, whereas AKT, ERK1/2, p38 MAPK were variably affected by sPLA2 IIa inhibition. NF-κB inhibitor-associated apoptosis confirmed the dominant role of NF-κB.
  
  
  CONCLUSIONS
  sPLA2 IIa attenuates growth and promotes apoptosis predominantly via its effects on NF-κB activity.
authors.affiliation: Department of Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Yu
authors.forename: Shana
authors.initials: S
authors.lastname: Kalatardi
authors.forename: John
authors.initials: J
authors.lastname: Dohse
authors.forename: Miral R
authors.initials: MR
authors.lastname: Sadaria
authors.forename: Xianzhong
authors.initials: X
authors.lastname: Meng
authors.forename: David A
authors.initials: DA
authors.lastname: Fullerton
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weyant
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D054497:Phospholipases A2, Secretory / Q000037:antagonists & inhibitors*; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D054497:Phospholipases A2, Secretory