Browse by author
Lookup NU author(s): Dr Frida Ponthan
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Neuroblastoma is the single most common and deadly tumor of childhood and is often associated with therapy resistance. Cyclooxygenases (COXs) catalyze the conversion of arachidonic acid to prostaglandins. COX-2 is up-regulated in several adult epithelial cancers and is linked to proliferation and resistance to apoptosis. We detected COX-2 expression in neuroblastoma primary tumors and cell lines but not in normal adrenal medullas from children. Treatment of neuroblastoma cells with nonsteroidal anti-inflammatory drugs, inhibitors of COX, induced caspase-dependent apoptosis via the intrinsic mitochondrial pathway. Treatment of established neuroblastoma xenografts in nude rats with the dual COX-1/COX-2 inhibitor diclofenac or the COX-2-specific inhibitor celecoxib significantly inhibited tumor growth in vivo (P < 0.001). In vitro, arachidonic acid and diclofenac synergistically induced neuroblastoma cell death. This effect was further pronounced when lipooxygenases were simultaneously inhibited. Proton magnetic resonance spectroscopy ((1)H MRS) of neuroblastoma cells treated with COX inhibitors demonstrated accumulation of polyunsaturated fatty acids and depletion of choline compounds. Thus, (1)H MRS, which can be performed with clinical magnetic resonance scanners, is likely to provide pharmacodynamic markers of neuroblastoma response to COX inhibition. Taken together, these data suggest the use of nonsteroidal anti-inflammatory drugs as a novel adjuvant therapy for children with neuroblastoma.
Author(s): Johnsen JI, Lindskog M, Ponthan FM, Pettersen I, Elfman L, Orrego A, Sveinbjörnsson B, Kogner P
Publication type: Article
Publication status: Published
Journal: Cancer Research
Year: 2004
Volume: 64
Issue: 20
Pages: 7210-7215
ISSN (print): 0008-5472
ISSN (electronic): 1538-7445
URL: http://dx.doi.org/10.1158/0008-5472.CAN-04-1795
DOI: 10.1158/0008-5472.CAN-04-1795
Notes: Journal Article Research Support, Non-U.S. Gov't United States
Altmetrics provided by Altmetric
