title: Docosahexaenoic acid, G protein-coupled receptors, and melanoma: is G protein-coupled receptor 40 a potential therapeutic target?
abstract: BACKGROUND
  To determine the effect of docosahexaenoic acid (DHA) on the growth of human melanoma in vitro and in vivo and to better understand the potential role of the G protein-coupled receptors (GPRs) in mediating this effect.
  
  
  METHODS
  For in vitro studies, human melanoma and control fibroblast cells were treated with DHA and TAK-875 (selective GPR40 agonist) and a cell viability assay was performed to determine cell counts. A murine subcutaneous xenograft model of human melanoma was used to test the effect of dietary treatment with an omega-3 fatty acid (FA) rich diet compared with an omega-6 FA rich diet on the growth of human melanoma in vivo. A similar animal model was used to test the effect of oral TAK-875 on the growth of established melanoma tumors in vivo.
  
  
  RESULTS
  DHA has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals on the omega-3 FA rich diet were 69% smaller in weight (P = 0.005) and 76% smaller in volume compared with tumors from animals on the omega-6 FA rich diet. TAK-875 has an inhibitory effect on the growth of human melanoma both in vitro and in vivo. Tumors from animals treated with TAK-875 were 46% smaller in weight (P = 0.07), 62% smaller in volume (P = 0.03), and grew 77% slower (P = 0.04) compared with the placebo group.
  
  
  CONCLUSIONS
  DHA and TAK-875 have a profound and selective inhibitory effect on the growth of human melanoma both in vitro and in vivo.
authors.affiliation: Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Deepika
authors.initials: D
authors.lastname: Nehra
authors.affiliation: Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts.
authors.forename: Amy H
authors.initials: AH
authors.lastname: Pan
authors.affiliation: Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Hau D
authors.initials: HD
authors.lastname: Le
authors.affiliation: Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Fallon
authors.affiliation: Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Carlson
authors.affiliation: Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Kalish
authors.affiliation: Department of Surgery and the Vascular Biology Program, Children's Hospital Boston, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts. Electronic address: mark.puder@childrens.harvard.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Puder
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004281:Docosahexaenoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008546:Melanoma, Experimental / Q000178:diet therapy* / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D001572:Benzofurans; C473034:FFAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D013450:Sulfones; C557331:TAK-875; D004281:Docosahexaenoic Acids
keywords: Docosahexaenoic acid; G protein–coupled receptor; GPR120; GPR40; Melanoma; Omega-3 fatty acid; Omega-3 polyunsaturated fatty acid