Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2115099 | Cancer Letters | 2007 | 8 Pages |
Abstract
Epstein-Barr Virus (EBV) is involved in the progression of lymphomas through still unknown mechanism involving increased resistance to induced apoptosis. We show here that in a set of apoptosis-resistant EBV-converted Burkitt's lymphoma clones, 5- and 12-lipoxygenases (LOXs) are over-expressed. Further investigations on 5-LOX showed that resistance to apoptosis increases parallely with the expression of 5-lipoxygenase (5-LOX). Inhibitors of 5-LOX: (a) decrease peroxides level, indicating that this enzyme promotes the generation of oxidative stress in EBV+ cells, and (b) potently induce apoptosis in the EBV resistant cell line E2R. 5- and 15-HETE, the products of the 5 and 15-LOXs, respectively, counteract 5-LOX inhibitor induced apoptosis, indicating that products of arachidonate metabolism, rather than peroxides, trigger a signal transduction that is required for survival of the EBV-converted cells. These findings suggest that 5- and, to a lesser extent, other LOXs, that are involved in tumor progression of several cell types, may also participate in lymphomagenesis, especially that EBV-mediated.
Keywords
IAPLOXsLMP1DCFH-DANOSNDGACAPENF-κBCOXROSquantitative RT-PCRnordihydroguaiaretic acidhydroxyeicosatetraenoic acidEBVLOXFlapApoptosisLymphoma cellscyclo-oxygenasenuclear factor kBBurkitt’s lymphomalipoxygenaseinhibitor of apoptosis proteinnitric oxide synthaseHETEEpstein–Barr virusPeroxidesLatent membrane protein 15-Lipoxygenase activating proteinReactive oxygen species
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Authors
Maria Cristina Belfiore, Alessandro Natoni, Roberta Barzellotti, Nicolo' Merendino, Gloria Pessina, Lina Ghibelli, Giampiero Gualandi,