Anticancer Effects of Nervonic Acid in Triple-Negative Breast Cancer.

Abstract

Triple-negative breast cancer (TNBC) has no therapeutic target; therefore, treatment is restricted to anticancer agents. However, TNBC is highly drug-resistant, meaning that novel therapeutic drugs for TNBC are required. Fatty acids can both inhibit and promote different cancers. Nervonic acid (NA) is a monovalent unsaturated fatty acid with anti-inflammatory effects, although its effect on cancer is unknown. Therefore, this study investigated the effect of NA on TNBC. BT-549 cells, a TNBC cell line, were exposed to different concentrations of NA (1, 10, 100, and 1000 µM) or a control (dimethylsulfoxide). In addition, 9-week-old, female BALB/cSlc-nu/nu mice had a BT-549 cell transplant into the right side of the fourth mammary fat pad before being administered NA (100 mg/kg) or sterile tap water for 1 week. Increasing NA concentrations reduced the viability of BT-549 cells. At 100 µM, NA increased the expression of single-stranded DNA, a marker of apoptosis; decreased the expression of nuclear factor-κ B, an apoptosis inhibitor; and decreased the expression of Ki-67, a marker of proliferation. Furthermore, 10 µM NA inhibited cell migration and invasion of BT-549 cells via a non-significant increase in the mRNA expression of E-cadherin (CDH1) and significant decreases in the mRNA expression of N-cadherin (CDH2) and the protein expression of matrix metalloproteinase-9 and 2. In addition, the growth and metastasis to the lungs of mammary gland tumors were significantly lower in NA-treated mice than in control mice. These results suggest that NA has an antitumor effect both in vitro and in vivo; therefore, NA may be a novel therapeutic agent for TNBC.