Effect of ω-3 and ω-9 fatty acid rich oils on lipoxygenases and cyclooxygenases enzymes and on the growth of a mammary adenocarcinoma model

Abstract

Background: Nutritional factors play a major role in cancer initiation and development. Dietary polyunsaturated fatty acids (PUFAs) have the ability to induce modifications in the activity of lipoxygenase (LOX) and cyclooxygenase (COX) enzymes that affect tumour growth. We studied the effect of two diets enriched in 6% Walnut and Peanut oils that are rich in ω-3 and ω9 PUFAs respectively on a murine mammary gland adenocarcinoma as compared with the control (C) that received commercial diet.

Results: Peanut oil enriched diet induced an increase in membrane arachidonic acid (AA) content and the cyclooxygenase enzyme derived 12-HHT (p < 0.05) and simultaneously showed decrease in 12-LOX, 15-LOX-2, 15-LOX-1 and PGE activities (p < 0.05) that corresponded to higher apoptosis and lower mitosis seen in this group (p < 0.05). Furthermore, Peanut oil group showed lower T-cell infiltration (p < 0.05), number of metastasis (p < 0.05) and tumour volume (p < 0.05) and longer survival rate compared to other groups.

Conclusions: The results of the present study showed that Peanut oil-enriched diet protects against mammary cancer development by modulating tumour membrane fatty acids composition and LOX and COX enzyme activities.

Figure 1

Membrane Fatty acids profile of commercial standards A) and TC obtained from murine mammary adenocarcinoma cells of mice fed with Control diet B) or basic diet enrichment with Walnut oil C) or Peanut oil D).

Figure 2

Different parameters of tumour development and metastasis from M3 hosts fed on Control, Walnut and Peanut diets. Different letters represent significant differences (p < 0.05): a) Tumour volume recorded during necropsy at 35 days after inoculation. Used as volume = tumour height × width × height. Values represent the mean ± SEM of 18 samples. b) Metastasis number of M3 host fed on diets. Values represent the mean ± SEM of 18 samples. c) Survival evaluation of M3 hosts fed on Control, Walnut and Peanut diets. Values represent the mean ± SEM of 10 animals. Different letters represent significant differences (p < 0.05).

Figure 3

a) Apoptotic cells in tumor cell suspension as determined by Flow cytometry using Annexin V/Propidium iodide double staining. Values represent the mean ±SEM of six samples. Different letters represent significant differences (p<0.05).b) Flow cytometry graphics show the apoptotic cells populations in tumor cells suspensions in the different diet conditions (circle areas). c) Mitotic and d) apoptotic figures (arrows) on neoplastic tumor tissue fixed in 10% neutral formalin, dehydrated and embedded in paraffin and stained with hematoxylin and eosin (arrows, H&E, 400 ×).

Figure 4

Different eicosanoids released from M3 TC of hosts fed on different diets after stimulation with ionophore A 23287 (2 M). Values represent the means ± SEM of 15 samples. Different letters represent significant differences (p < 0.05): a) 12 (S)-HHT; b) PGE₂; c) 12 (S)-HETE; d) 15 (S)-HETE; e) 13 (S)-HODE and f) 13 (S)-HODE/12 (S)-HETE ratio.