title: Inhibition of neuroblastoma cell proliferation with omega-3 fatty acids and treatment of a murine model of human neuroblastoma using a diet enriched with omega-3 fatty acids in combination with sunitinib.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  These findings suggest a potential role for ω-3 PUFAs in the combination treatment of neuroblastoma.
  
  
  METHODS
  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.
authors.affiliation: Vascular Biology Program, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Carmen M
authors.initials: CM
authors.lastname: Barnés
authors.forename: Daniela
authors.initials: D
authors.lastname: Prox
authors.forename: Emily A
authors.initials: EA
authors.lastname: Christison-Lagay
authors.forename: Hau D
authors.initials: HD
authors.lastname: Le
authors.forename: Sarah
authors.initials: S
authors.lastname: Short
authors.forename: Flavia
authors.initials: F
authors.lastname: Cassiola
authors.forename: Dipak
authors.initials: D
authors.lastname: Panigrahy
authors.forename: Deviney
authors.initials: D
authors.lastname: Chaponis
authors.forename: Catherine
authors.initials: C
authors.lastname: Butterfield
authors.forename: Deepika
authors.initials: D
authors.lastname: Nehra
authors.forename: Erica M
authors.initials: EM
authors.lastname: Fallon
authors.forename: Mark
authors.initials: M
authors.lastname: Kieran
authors.forename: Judah
authors.initials: J
authors.lastname: Folkman
authors.forename: Mark
authors.initials: M
authors.lastname: Puder
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000378:metabolism; D005395:Fish Oils / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D016513:Mice, SCID; D055806:Microvessels / Q000187:drug effects / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D009447:Neuroblastoma / Q000098:blood supply / Q000178:diet therapy* / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D000077210:Sunitinib; D013997:Time Factors; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; C033266:Menhaden oil; D016718:Arachidonic Acid; D000077210:Sunitinib