5‐Lipoxygenase regulates malignant mesothelial cell survival: involvement of vascular endothelial growth factor

• DOI: 10.1096/fj.01-0150com
• Publication Date: 2002-07-26T19:03:24Z
• Authors: Mario Romano; ALFONSO CATALANO; MICHELE NUTINI; ETRUSCA D'URBANO; CARLO CRESCENZI; JOAN CLARIA; ROBERTA LIBNER; GIOVANNI DAVI; ANTONIO PROCOPIO
• Keywords: Mesothelioma; Lymphokines; 0303 health sciences; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Cell Survival; Green Fluorescent Proteins; Apoptosis; Endothelial Growth Factors; DNA, Antisense; Gene Expression Regulation, Enzymologic; Cell Line; Luminescent Proteins; 03 medical and health sciences; Gene Expression Regulation; Mutation; Benzoquinones; Humans; Masoprocol; Lipoxygenase Inhibitors; Promoter Regions, Genetic; Cell Division

Evidence indicates that lipoxygenases (LO) may play a role in cancer cell survival. We show human malignant pleural mesothelial (MM) cells, but not normal (NM) express catalytically active 5-LO. Pharmacological or genetic inhibition of MM 5-LO determined nucleosome formation and induced DNA fragmentation pattern typical apoptosis. This was completely reversed by exogenously added 5(S)-HETE 12(S)-, 15(S)-HETE, leukotriene (LT)B4. A antisense oligonucleotide potently time-dependently reduced vascular endothelial growth factor (VEGF) mRNA constitutive VEGF accumulation the conditioned media cells. When NM cells were transfected with cDNA, basal arachidonic acid-induced increased consistently 6- 12-fold, respectively. associated significant increase synthesis counteracted specific anti-VEGF antibody. Arachidonic acid also stimulated activity promoter construct. Thus, is key regulator proliferation survival via VEGF-related circuit.