Effects of dietary fish oil on fatty acids and eicosanoids in metastasizing human breast cancer cells

Abstract

We examined the relationships between the suppressive effects of dietary fish oil on growth and metastasis of MDA-MB-435 human breast cancer cells in female nude mice and the primary tumor phospholipid fatty acid concentrations, phospholipase A2 activity, and eicosanoid levels. Mice (n = 120) were fed a 23% (wt/wt) corn oil (CO) linoleic acid (LA)-rich diet for seven days before and after 10(6) tumor cells were injected into a mammary fat pad, and then the mice receive one of three isocaloric diets containing 23% total fat but different proportions of CO and menhaden oil (MO) (18% CO-5% MO, 11.5% CO-11.5% MO, 5% CO-18% MO) or a 23% fat diet containing 18% deodorized fish oil supplemented with tocopherol and tert-butylhydroquinone antioxidants (FAO). Primary tumor growth rate was significantly greater in mice fed the 18% CO diet than in the three diets containing higher levels of fish oil (all p < 0.05). The 18% MO diet, but not the 11.5% MO or the 18% FAO diet, suppressed the development of lung metastases compared with the 18% CO diet. Increasing the proportion of MO relative to CO in the diets produced corresponding increases in the primary tumor phospholipid eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) concentrations and reductions in LA and arachidonic acid. There was a significant positive correlation between the LA concentration in these tumors and the extent of lung metastasis (r = 0.504). Tumor phospholipase A2 activity was unaffected by dietary MO intake. Prostaglandin E2 concentration was inversely correlated with phospholipid EPA (r = -0.484) and DHA (r = -0.439), but there was no relationship with lung metastasis. Tumor leukotriene B4 and 5-hydroxyeicosatetraenoic acid levels were not reduced by dietary MO. The 18% FAO- and the 18% MO-fed mice showed similar relationships for the phospholipid fatty acids and prostaglandin E2, despite the lack of effect on metastasis. The strong correlation between phospholipid LA levels and metastasis and the lack of an association with tumor eicosanoids suggest that the 18% MO diet inhibited metastasis because dietary LA was replaced by other fatty acids.

The Linoleic Acid Metabolite, (13S)-Hydroperoxyoctadecadienoic Acid, Augments the Epidermal Growth Factor Receptor Signaling Pathway by Attenuation of Receptor Dephosphorylation

“…A risk factor associated with the etiology of breast cancer arises from animal and human epidemiology studies linking high dietary fat with increased incidence of breast cancer. Linoleic acid is the major polyunsaturated fatty acid consumed in the human diet and has been demonstrated to stimulate cell proliferation and metastasis in human breast carcinoma cells (38,39). Our investigation indicates that linoleic acid metabolism may play a central role in transduction of the EGF mitogenic signal from the cell surface to the nucleus and may provide a useful model for understanding neoplastic progression at a molecular level.…”

Dietaryω-3 Polyunsaturated Fatty Acid DHA: A Potential Adjuvant in the Treatment of Cancer

“…As early as 1994, Rose et al started a certain number of studies on the effects of dietary fish oil ω -3 PUFAs, including DHA, on the growth and metastases of MDA-MB-435 human breast cancer cells in female nude mice [82]. Animals were fed with three isocaloric diets containing 23% total fat but different proportion of corn oil (rich in linoleic acid-LA) and menhaden oil (rich in EPA and DHA) [65, 82].…”

“…Animals were fed with three isocaloric diets containing 23% total fat but different proportion of corn oil (rich in linoleic acid-LA) and menhaden oil (rich in EPA and DHA) [65, 82]. The authors reported that, in contrast to mice fed with diets rich in LA, mice receiving diets supplemented with EPA or DHA showed a significant suppression of both primary tumor growth rate and lung metastasis occurrence and severity, suggesting a role for EPA and DHA in the inhibition not only of tumor growth but also of metastasization of human breast cancer cells [82, 83]. Successively, the same authors investigated tumor responses to EPA or DHA administered immediately after surgical excision of the primary tumor (“postoperative adjuvant” activity).…”

A Multiethnic Cohort in Hawaii and Los Angeles: Baseline Characteristics

“…For example, some researchers have suggested that soy products, because of their content of isoflavones such as genistein and daidzein, may be protective against breast and prostate cancers (47,48); there are limited data to support the hypothesis (49,50). Similarly, a high intake of the omega-3 polyunsaturated fats found in fish has been postulated to protect against cancer (51). Native Hawaiian men have the highest intake of fish and a relatively high intake of tofu, and their rate of prostate cancer is the lowest of the five ethnic groups.…”