Docosahexaenoic acid alters cell death, cancer and cell‐cycle signaling networks in breast cancer cell lines

Abstract

Long‐chain n‐3 polyunsaturated fatty acids reduce viability of breast cancer cells. While the products of several genes are altered, the changes in gene expression responsible for these antitumor effects have not been clearly established. The objective of this study was to measure alterations in gene expression in breast cancer cells treated with docosahexaenoic (DHA) and eicosapentaneoic (EPA) acid. MDA‐MB‐231 (estrogen receptor, ER‐) and MCF‐7 (ER+) human breast cancer cells were treated with control media, 100 μM linoleic acid, DHA or EPA for 48 h. Gene expression was analyzed using Affymetrix GeneChip Human Gene ST 1.0 microarray chips and data analyzed using Partek Genomics Suite and Ingenuity Pathway Analysis. Principal Component Analysis revealed that treatment accounted for 40% of the alteration in gene expression in both cell lines. Compared to control, fatty acids changed networks of lipid metabolism and small molecule biochemistry (P<0.05). DHA altered cancer, cell death and tumor morphology cellular signaling networks, compared with other conditions, while EPA impacted an array of non‐cancer related networks (P<0.05). A number of previously unidentified genes were differentially expressed in response to DHA treatment. This study provides an understanding of the genomic changes induced by n‐3 PUFA in breast cancer cells. Funding from CIHR and JBE received a CIHR postdoctoral fellowship.