|Authors||Barnés CM, Prox D, Christison-Lagay EA, Le HD, Short S, Cassiola F, Panigrahy D, Chaponis D, Butterfield C, Nehra D, Fallon EM, Kieran M, Folkman J, Puder M|
|Journal||Pediatr. Res. Volume: 71 Issue: 2 Pages: 168-78|
|Publish Date||2012 Feb|
We investigated the use of dietary omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) in the treatment of neuroblastoma both as a sole agent and in combination with sunitinib, a broad-spectrum tyrosine kinase receptor inhibitor.Substitution of all dietary fat with menhaden oil (ω-3 PUFA rich) resulted in a 40-70% inhibition of tumor growth and a statistically significant difference in the levels of several PUFAs (18:2 ω-6, 20:4 ω-6, 22:4 ω-6, 20:5 ω-3) as compared with a control diet. Furthermore, tumors from animals on the ω-3 fatty acid (FA)-enriched diet had an elevated triene/tetraene ratio suggestive of a change in local eicosanoid metabolism in these tissues similar to that seen with essential fatty acid deficiency. The ω-3 FA-enriched diet also decreased tumor-associated inflammatory cells and induced mitochondrial changes suggestive of mitochondrial damage. Combination treatment with sunitinib resulted in further reduction in tumor proliferation and microvessel density.These findings suggest a potential role for ω-3 PUFAs in the combination treatment of neuroblastoma.We used a murine model of orthotopic and subcutaneous human neuroblastoma and diets that differ in the FA content to define the optimal dietary ω-3/omega-6 (ω-6) FA ratio required for the inhibition of these tumors.