Group IIa sPLA2 Inhibition Attenuates NF-κB Activity and Promotes Apoptosis of Lung Cancer Cells

• Published in: Anticancer research Vol. 32; no. 9; pp. 3601 - 3607
• Main Authors: YU, Jessica A, KALATARDI, Shana, DOHSE, John, SADARIA, Miral R, MENG, Xianzhong, FULLERTON, David A, WEYANT, Michael J
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-09-2012
• Subjects: Apoptosis - drug effects; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - enzymology; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Growth Processes - drug effects; Cell Line, Tumor; Enzyme Inhibitors - pharmacology; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; NF-kappa B - metabolism; Phospholipases A2, Secretory - antagonists & inhibitors; Phosphorylation - drug effects; Pneumology; Tumors; Tumors of the respiratory system and mediastinum; Lung disease; Secretory phospholipase A2; NCI-H358 cells; Enzyme; Respiratory disease; Lung cancer; A549; Esterases; Malignant tumor; Phospholipase A; Biological activity; Carboxylic ester hydrolases; NF-κB; Cancerology; Cell death; Hydrolases; Bronchus disease; Inhibitor; Transcription factor NFκB; Tumor cell; Cancer; Apoptosis
• ISSN: 0250-7005; 1791-7530

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.