Anticancer Research 2012-09-01

Group IIa sPLA2 inhibition attenuates NF-κB activity and promotes apoptosis of lung cancer cells.

Jessica A Yu, Shana Kalatardi, John Dohse, Miral R Sadaria, Xianzhong Meng, David A Fullerton, Michael J Weyant

Index: Anticancer Res. 32(9) , 3601-7, (2012)

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Abstract

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).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.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.sPLA2 IIa attenuates growth and promotes apoptosis predominantly via its effects on NF-κB activity.