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

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.