n-3 and n-6 fatty acid processing and growth effects in neoplastic and non-cancerous human mammary epithelial cell lines

Abstract

The type rather than the amount of dietary fat may be more important in breast carcinogenesis. While animal studies support this view, little is known about the effects of essential fatty acids (EFAs) at the cellular level. The MCF-7 breast cancer and the MCF-10A non-cancerous human mammary epithelial cell lines are compared in terms of growth response to EFAs and ability to incorporate and process the EFAs. Eicosapentaenoic (EPA, n-3) and docosahexaenoic (DHA, n-3) acids, presented bound to albumin, inhibited the growth of MCF-7 cells by as much as 50% in a dose-dependent manner (6-30 microM) in medium containing 0.5% serum. alpha-Linolenic (LNA, n-3) and arachidonic (AA, n-6) acids inhibited growth less extensively, while linoleic acid (LA, n-6) had no effect. In contrast, MCF-10A cells were not inhibited by any of the EFAs at levels below 24 microM. The differential effects of AA, EPA and DHA on MCF-7 and MCF-10A cells support a protective role of highly unsaturated essential fatty acids against breast cancer. The EFAs were primarily incorporated into phosphoglycerides. MCF-7 cells showed chain elongations and possibly delta 8 desaturation, but no AA was formed from LA, nor EPA or DHA from LNA. In contrast, MCF-10A cells desaturated and elongated the exogenous EFAs via all the known pathways. These findings suggest defects in the desaturating enzymes of MCF-7 cells. LNA, DHA and AA presented to MCF-7 cells in phospholipid liposomes inhibited growth as extensively as albumin-bound free acids, but were less extensively incorporated, suggesting different mechanisms of inhibition for the two methods.

Breast cancer risk and erythrocyte compositions of n‐3 highly unsaturated fatty acids in Japanese

“…27,47,48 In postmenopausal women in cohort studies, decreased risk was associated with higher compositions of n-6 PUFAs and 18:2n-6, but not AA. 26,48 The AA cascade is suggested to play critical roles in tumor development from laboratory studies, [1][2][3]6 but an inverse association with breast cancer risk was unexpectedly here found for erythrocyte composition of AA. On the other hand, erythrocyte ratios of AA/EPA and AA/ DHA had positive links with risk and the findings support the hypothesis regarding competitive inhibition for biosynthesis of AAderived eicosanoids such as prostaglandin E 2 .…”

“…Feeding studies with dietary supplementation of fish, fish oil, EPA and DHA have confirmed corresponding changes in biomate- One case and eight control subjects were excluded from analyses (see Table 1). ORs and their 95% CIs were adjusted for BMI (continuous), habitual exercise, drinking and smoking status, green-yellow vegetable intake (g/1000 kcal), menopausal status (pre-or post-menopause), family history of breast cancer in parents and/or siblings (yes or no), age at menarche ( 12, 13-14 or 15 years), menopausal periods (continuous), parity (0, 1, 2 or 3) and hormone users (yes or no).-2 Meat included beef, pork and poultry.- 3 Dietary intakes of each fatty acid group were explained in ''Material and methods'' and mainly composed of the selected 13 fatty acids as follows; SFAs (saturated fatty acids) 5 14:0 1 16:0 1 18:0; MUFAs (monounsaturated fatty acids) 5 16:1n-7 1 18:1n-9; PUFAs (polyunsaturated fatty acids) 5 n-6 PUFAs 1 n-3 PUFAs; n-6 PUFAs 5 18:2n-6 1 18:3n-6 1 20:3n-6 1 20:4n-6 (arachidonic acid, AA); n-3 PUFAs 5 18:3n-3 1 n-3 highly unsaturated fatty acids (HUFAs); and n-3 HUFAs 5 20:5n-3 (eicosapentaenoic acid, EPA) 1 22:5n-3 1 22:6n-3 (docosahexaenoic acid, DHA). NS; Not significant.…”

“…[1][2][3] n-3 PUFAs in our diets include both a-linolenic acid (18:3n-3) as a vegetable oil and n-3 highly unsaturated fatty acids (HUFAs), such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), generally of marine origin. Especially, ecological studies have suggested that higher intake of fish rich in n-3 HUFAs is correlated with a lower cancer incidence in several sites.…”

Effects of iron supplementation and ET-18-OCH3 on MDA-MB 231 breast carcinomas in nude mice consuming a fish oil diet

“…Results of previous studies using either cultured cells (examples : Begin et al, 1986;Canuto et al, 1991;Grammatikos et al, 1994;Maehle et al, 1995;Padma and Das, 1996) or whole animals (examples: Borgeson et al, 1989;Pritchard et al, 1989; Gonzalez et al, 1991; have indicated that an increased exposure to the types of HPUFAs found in fish oil, especially eicosapentanoic acid, kills a variety of cancer cells without killing normal cells, and that addition of an iron-containing compound may increase cell death. However, the question still remains as to whether the most important cause of tumour regression and cell death is: (1) induction of lipid peroxidation; (2) alteration of eicosanoid production; (3) some other mechanisms associated with the alteration in membrane fatty acids or (4) the addition of iron to the diet or culture media.…”

Optimizing Dietary Fat to Reduce Breast Cancer Risk: Are we there Yet?

“…Treatment of MCF-10A cells with 6-30 μM linolenate had largely no effect, although a decrease in viability was observed at the highest concentration. The effect was observed whether linolenate was supplied as a free fatty acid bound to albumin, or as a phospholipid enriched lysosome [80]. 25-100 μM linolenate also decreased the proliferation of the MDA-MB-231 breast cancer cells in a dose dependent manner [81].…”