PMID- 22993297 OWN - NLM STAT- MEDLINE DCOM- 20130104 LR - 20120920 IS - 1791-7530 (Electronic) IS - 0250-7005 (Linking) VI - 32 IP - 9 DP - 2012 Sep TI - Group IIa sPLA2 inhibition attenuates NF-kappaB activity and promotes apoptosis of lung cancer cells. PG - 3601-7 AB - BACKGROUND/AIM: 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-kappaB). MATERIALS AND 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-kappaB signaling pathways were investigated. RESULTS: sPLA2 IIa inhibition reduced proliferation and increased apoptosis. NF-kappaB activity was attenuated, whereas AKT, ERK1/2, p38 MAPK were variably affected by sPLA2 IIa inhibition. NF-kappaB inhibitor-associated apoptosis confirmed the dominant role of NF-kappaB. CONCLUSION: sPLA2 IIa attenuates growth and promotes apoptosis predominantly via its effects on NF-kappaB activity. FAU - Yu, Jessica A AU - Yu JA AD - Department of Surgery, University of Colorado School of Medicine, Aurora, CO 80045, USA. FAU - Kalatardi, Shana AU - Kalatardi S FAU - Dohse, John AU - Dohse J FAU - Sadaria, Miral R AU - Sadaria MR FAU - Meng, Xianzhong AU - Meng X FAU - Fullerton, David A AU - Fullerton DA FAU - Weyant, Michael J AU - Weyant MJ LA - eng PT - Journal Article PL - Greece TA - Anticancer Res JT - Anticancer research JID - 8102988 RN - 0 (Enzyme Inhibitors) RN - 0 (NF-kappa B) RN - EC 3.1.1.4 (Phospholipases A2, Secretory) SB - IM MH - Apoptosis/*drug effects MH - Carcinoma, Non-Small-Cell Lung/drug therapy/enzymology/*metabolism/pathology MH - Cell Growth Processes/drug effects MH - Cell Line, Tumor MH - Enzyme Inhibitors/*pharmacology MH - Humans MH - Lung Neoplasms/drug therapy/enzymology/*metabolism/pathology MH - NF-kappa B/*metabolism MH - Phospholipases A2, Secretory/*antagonists & inhibitors MH - Phosphorylation/drug effects EDAT- 2012/09/21 06:00 MHDA- 2013/01/05 06:00 CRDT- 2012/09/21 06:00 PHST- 2012/09/21 06:00 [entrez] PHST- 2012/09/21 06:00 [pubmed] PHST- 2013/01/05 06:00 [medline] AID - 32/9/3601 [pii] PST - ppublish SO - Anticancer Res. 2012 Sep;32(9):3601-7.