Abstract 2600: Polyunsaturated omega-3 fatty acids and their metabolites preferentially inhibit cell proliferation and motility in triple negative over luminal breast cancer cells.

Abstract

Abstract The role of diet as a preventive measure in breast cancer remains controversial. Current literature suggests that the risk of developing breast cancer may decrease or increase with the intake of omega-3 (n-3) and omega-6 (n-6) fatty acids, respectively. Omega 3 polyunsaturated fatty acids (PUFAs) exert an anticancer effect by affecting multiple cellular mechanisms leading to inhibition of proliferation and induction of apoptosis. It is well known that breast cancer comprises distinct molecular subtypes which differ in their responsiveness to therapeutic and preventive agents. In these experiments, we tested the hypothesis that n-3FA may preferentially affect triple negative breast cancer cells for which no targeted intervention is presently available. The in vitro effects of n-3 PUFA Docosahexaenoic acid (DHA) and its metabolites, 4-OH-DHA and 4-OXO-DHA, were tested on proliferation and motility of seven triple negative human basal breast cell lines at different stages of transformation (MCF-10F, trMCF, bsMCF, caMCF, MDA-MB-231, Hs-578T, and BT-549), and three luminal breast cancer cell lines (MCF-7, T-47D, and SK-BR-3). Cell proliferation was measured with the tetrazolium MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and cell migration was assessed using the wound healing assay via time lapse microscopy with MetaMorph 7.7.7.8. All assays were performed in quadruplicate. Statistical significance was assessed using Student's t-test (p<0.05). DHA and its metabolites significantly inhibited cell proliferation (20-90% reduction) of both basal and luminal breast cancer cell lines. The inhibitory effect was more pronounced on triple negative basal breast cancer cell lines as compared to luminal breast cancer cell lines. DHA did not produce an inhibitory effect on cell migration. However, the metabolites of DHA significantly reduced (20-60% reduction) cell migration on the bsMCF cell line. Our data provide novel information regarding the preferential antitumor effect of DHA and its metabolites on basal type breast cancer. (This project was supported by the Komen Foundation (KG081632). Citation Format: Thomas J. Pogash, Ricardo Lopez de Cicco, Benjamin Pressly, Irma H. Russo, Julie A. Himmelberger, Shantu Amin, Krishne Gowda, Karam El-Bayoumy, Andrea Manni, Jose Russo. Polyunsaturated omega-3 fatty acids and their metabolites preferentially inhibit cell proliferation and motility in triple negative over luminal breast cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2600. doi:10.1158/1538-7445.AM2013-2600