Dietary Omega-3 Fatty Acids, Cell-Mediated Cytotoxicity and Anti-Tumorigenic Activity in Balb/c Mice

Abstract

Two animal model systems were used to evaluate the effects of an increased consumption of 18:3n-3: cell-mediated cytotoxic (CMC) activity and tumor growth. The most likely mechanism by which dietary 18:3n-3 will alter CMC and tumor growth is through changes in eicosanoid production. One study demonstrated that feeding a diet containing 10% by weight linseed oil (LO), which contains over 50% 18:3n-3, significantly reduced prostaglandin (PG) and leukotriene production by immune cells. That natural and CMC activity after an immunochallenge was generally not altered by LO feeding was shown in a subsequent study. In this same study it was observed that CMC activity in the spleen 6 days after a vaccinia virus challenge was significantly greater in LO-fed compared to control mice fed corn oil (CO).

The time course for both the natural killer (NK)/natural cytotoxic (NC)-mediated and cytotoxic T-lymphocyte (CTL)-mediated responses to two suboptimal doses of virus was found to be similar for mice fed LO and CO. As in the previous study, CMC activity against vaccinia virus-infected target cells was significantly higher in mice fed LO than CO, 6 days post-challenge.

When mice were fed a LO diet for 2 months then switched to a CO diet, endogenous PG synthesis by PEC was elevated by 74% and by splenocytes by 37% after 4 days. Natural CMC in the peritoneum was significantly suppressed in mice switched to the CO diet, while splenic NK activity was unchanged.

When fish (menhaden) oil (FO) was utilized as a source of n-3 fatty acids, the reduction of PG synthesis exceeded that obtained for LO-feeding. NK activity in mice fed FO was significantly lower compared to CO-fed mice, although virus-stimulated activity was similar.

Dietary 18:3n-3 retarded the growth and metastatis of the highly metastatic mammary tumor cell line (410.4). Feeding FO had a 2-fold greater effect on tumor PG synthesis, yet did not significantly influence 410.4 growth or metastasis like LO-feeding. On the other hand, feeding FO and not LO, reduced the growth of the slower growing, less metastatic parent mammary tumor cell line (410). CMC activity in tumor-bearing mice was similarly suppressed in all dietary treatments, compared to tumor-free mice.