title: Synergistic anti-tumor effects of melatonin and PUFAs from walnuts in a murine mammary adenocarcinoma model.
abstract: OBJECTIVE
  The aim of this study was to determine the effects of some polyunsaturated fatty acids plus phytomelatonin from walnuts in the development of mammary gland adenocarcinoma.
  
  
  METHODS
  BALB/c mice were fed a semisynthetic diet supplemented with either 6% walnut oil and 8% walnut flour containing phytomelatonin (walnut diet: WD); or 6% corn oil plus commercial melatonin (melatonin diet: MD), or the control group (CD), which received only 6% of corn oil. Membrane fatty acids of tumor cells (TCs) were analyzed by gas liquid chromatography, cyclooxygenase (COX) and lipoxygenase (LOX) derivatives, and plasma melatonin by high-performance liquid chromatography; apoptosis and tumor-infiltrating lymphocytes by flow cytometry.
  
  
  RESULTS
  TCs from the MD and WD mice showed significant decreases in linoleic acid compared with the CD group (P < 0.05). Significantly lower levels of LOX-[13(S)-HODE] were found in TCs from the MD and WD group than in CD (P < 0.0001). COX-[12(S)-HHT] was lower and 12 LOX-[12(S)-HETE] was higher in TCs from the MD group than form the WD and CD arms (P < 0.05). Plasma melatonin, apoptosis, tumor infiltration, and survival time were significantly lower in CD mice than in MD and WD mice (P < 0.05).
  
  
  CONCLUSIONS
  This study shows that melatonin, along with polyunsaturated fatty acids, exerts a selective inhibition of some COX and LOX activities and has a synergistic anti-tumor effect on a mammary gland adenocarcinoma model.
authors.affiliation: Instituto de Biología Celular-Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: Carolina P
authors.initials: CP
authors.lastname: Garcia
authors.affiliation: Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Cátedra de Química Orgánica. FCEF y N. UNC, Argentina.
authors.forename: Alicia L
authors.initials: AL
authors.lastname: Lamarque
authors.affiliation: Instituto de Investigaciones en Ciencias de la Salud de Córdoba (INICSA-CONICET) and Cátedra de Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba (FCM-UNC), Ciudad Universitaria, Córdoba, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Comba
authors.affiliation: Instituto de Biología Celular-Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: María A
authors.initials: MA
authors.lastname: Berra
authors.affiliation: Instituto de Biología Celular-Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Argentina.
authors.forename: Renata A
authors.initials: RA
authors.lastname: Silva
authors.affiliation: Instituto Multidisciplinario de Biología Vegetal (IMBIV-CONICET), Cátedra de Química Orgánica. FCEF y N. UNC, Argentina.
authors.forename: Diana O
authors.initials: DO
authors.lastname: Labuckas
authors.affiliation: UND Life Sciences, Shaker Heights, Ohio, United States; Jawaharlal Nehru Technological University, Kakinada, India; Bio-Science Research Centre, Gayatri Vidya Parishad College of Engineering, Visakhapatnam, India.
authors.forename: Undurti N
authors.initials: UN
authors.lastname: Das
authors.affiliation: Instituto de Investigaciones en Ciencias de la Salud de Córdoba (INICSA-CONICET) and Cátedra de Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba (FCM-UNC), Ciudad Universitaria, Córdoba, Argentina.
authors.forename: Aldo R
authors.initials: AR
authors.lastname: Eynard
authors.affiliation: Instituto de Investigaciones en Ciencias de la Salud de Córdoba (INICSA-CONICET) and Cátedra de Biología Celular, Histología y Embriología, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba (FCM-UNC), Ciudad Universitaria, Córdoba, Argentina. Electronic address: Epasqual@cmefcm.uncor.edu.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Pasqualini
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D004032:Diet; D004195:Disease Models, Animal; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D031324:Juglans / Q000737:chemistry*; D019787:Linoleic Acid / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D008807:Mice, Inbred BALB C; D009754:Nuts / Q000737:chemistry*; D008517:Phytotherapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016861:Cyclooxygenase Inhibitors; D015525:Fatty Acids, Omega-3; D019787:Linoleic Acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D008550:Melatonin
keywords: Cancer; Diet; Eicosanoids; PUFAs; Phytomelatonin