Synergistic anti-tumor effects of melatonin and PUFAs from walnuts in a murine mammary adenocarcinoma model

Nutrition. 2015 Apr;31(4):570-7. doi: 10.1016/j.nut.2014.06.001. Epub 2014 Jun 23.

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.

Keywords: Cancer; Diet; Eicosanoids; PUFAs; Phytomelatonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / metabolism
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cyclooxygenase Inhibitors / pharmacology
  • Cyclooxygenase Inhibitors / therapeutic use
  • Diet
  • Disease Models, Animal
  • Drug Synergism
  • Fatty Acids, Omega-3 / pharmacology
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Juglans / chemistry*
  • Linoleic Acid / metabolism
  • Lipoxygenase / metabolism
  • Male
  • Melatonin / blood
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Mice, Inbred BALB C
  • Nuts / chemistry*
  • Phytotherapy*
  • Prostaglandin-Endoperoxide Synthases / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • Cyclooxygenase Inhibitors
  • Fatty Acids, Omega-3
  • Linoleic Acid
  • Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases
  • Melatonin