Differential Ratios of Omega Fatty Acids (AA/EPA+DHA) Modulate Growth, Lipid Peroxidation and Expression of Tumor Regulatory MARBPs in Breast Cancer Cell Lines MCF7 and MDA-MB-231.

Prakash P Mansara,Milind M Vaidya,Rashmi A Deshpande,Ruchika Kaul-Ghanekar,Clarissa Menezes Maya-Monteiro

doi:10.1371/journal.pone.0136542

Abstract

Omega 3 (n3) and Omega 6 (n6) polyunsaturated fatty acids (PUFAs) have been reported to exhibit opposing roles in cancer progression. Our objective was to determine whether different ratios of n6/n3 (AA/EPA+DHA) FAs could modulate the cell viability, lipid peroxidation, total cellular fatty acid composition and expression of tumor regulatory Matrix Attachment Region binding proteins (MARBPs) in breast cancer cell lines and in non-cancerous, MCF10A cells. Low ratios of n6/n3 (1:2.5, 1:4, 1:5, 1:10) FA decreased the viability and growth of MDA-MB-231 and MCF7 significantly compared to the non-cancerous cells (MCF10A). Contrarily, higher n6/n3 FA (2.5:1, 4:1, 5:1, 10:1) decreased the survival of both the cancerous and non-cancerous cell types. Lower ratios of n6/n3 selectively induced LPO in the breast cancer cells whereas the higher ratios induced in both cancerous and non-cancerous cell types. Interestingly, compared to higher n6/n3 FA ratios, lower ratios increased the expression of tumor suppressor MARBP, SMAR1 and decreased the expression of tumor activator Cux/CDP in both breast cancer and non-cancerous, MCF10A cells. Low n6/n3 FAs significantly increased SMAR1 expression which resulted into activation of p21WAF1/CIP1 in MDA-MB-231 and MCF7, the increase being ratio dependent in MDA-MB-231. These results suggest that increased intake of n3 fatty acids in our diet could help both in the prevention as well as management of breast cancer.

Highlights

Breast cancer is the most common malignancy and one of the leading cause of cancer-related deaths in women worldwide [1, 2]
It was found that upto 280 μM concentration, the individual fatty acids (EPA, Docosahexanoic acid (DHA) and arachidonic acid (AA)) were almost non-toxic to MCF10A, HEK 293 and HaCaT (Fig 1); as well as MDA-MB-231 and MCF7 (Fig 2)
We found that low ratios of n6/n3 fatty acids preferentially killed the breast cancer cells; modulated their lipid peroxidation and critically controlled the expression of tumor regulatory Matrix Attachment Region binding proteins (MARBPs)

Summary

Introduction

Breast cancer is the most common malignancy and one of the leading cause of cancer-related deaths in women worldwide [1, 2]. Several factors have shown promise in reducing breast cancer incidence rates wherein change in lifestyle, especially diet, has proven to be the most popular measure. EPA and DHA are essential fatty acids, which human body cannot synthesize and should be obtained from diet. AA, EPA and DHA occur in the diet in animal tissue lipids [14]. Fish oil is highly rich in EPA and DHA, and has been suggested for different populations due to health benefits [15]. We found that supplementation of fish oil capsules, containing EPA:DHA in the ratio of 1.5:1, in breast cancer patients undergoing chemotherapy, significantly improved their serum antioxidant levels as well as quality of life parameters [16]

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