NSAIDs in neuroblastoma therapy

Cyclooxygenases (COX) catalyse the conversion of arachidonic acid to prostaglandins. COX-2 is upregulated in several adult epithelial cancers. In neuroblastoma it has been shown that the majority of primary tumours and cell lines express high levels of COX-2, whereas normal adrenal medullas from chi...

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Bibliographic Details
Published in:Cancer letters 2005-10, Vol.228 (1), p.195-201
Main Authors: Johnsen, John I., Lindskog, Magnus, Ponthan, Frida, Pettersen, Ingvild, Elfman, Lotta, Orrego, Abiel, Sveinbjörnsson, Baldur, Kogner, Per
Format: Article
Language:English
Subjects:
Acids
Angiogenesis
Animals
Anti-Inflammatory Agents, Non-Steroidal - therapeutic use
Apoptosis
Cancer
Cancer therapies
Cyclooxygenase Inhibitors - therapeutic use
Cyclooxygenase-2
Cytotoxicity
Magnetic Resonance Spectroscopy
Medicin och hälsovetenskap
Neuroblastoma
Neuroblastoma - drug therapy
Neuroblastoma - enzymology
Neuroblastoma - pathology
Non-steroidal anti-inflammatory drugs
Proteins
Rats
Rats, Nude
Rodents
Studies
Therapy
Tumors
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Summary:Cyclooxygenases (COX) catalyse the conversion of arachidonic acid to prostaglandins. COX-2 is upregulated in several adult epithelial cancers. In neuroblastoma it has been shown that the majority of primary tumours and cell lines express high levels of COX-2, whereas normal adrenal medullas from children do not express COX-2. Treatment of neuroblastoma cells with nonsteroidal anti-inflammatory drugs (NSAIDs), inhibitors of COX, induces caspase-dependent apoptosis via the intrinsic mitochondrial pathway. Established neuroblastoma xenografts in nude rats treated with the dual COX-1/COX-2 inhibitor, diclofenac, or the COX-2 specific inhibitor, celecoxib significantly inhibits neuroblastoma growth in vivo. In vitro, arachidonic acid and diclofenac synergistically induces neuroblastoma cell death. This effect is further pronounced when lipoxygenases is inhibited simultaneously. Proton MR-spectroscopy ( 1H MRS) of neuroblastoma cells treated with COX-inhibitors demonstrates accumulation of polyunsaturated fatty acids and depletion of choline compounds. Thus, 1H MRS, which can be performed with clinical MR-scanners, is likely to provide pharmacodynamic markers of neuroblastoma response to COX-inhibition. Taken together, these data suggest the use of NSAIDs as a novel adjuvant therapy for children with neuroblastoma.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2005.01.058