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Updated: May 17, 2025

Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Anticancer Effects of Nervonic Acid in Triple-Negative Breast Cancer
Akiho Kawai1, Fumiaki Ono2, Takao Satou2
1Graduate School of Agricultural and Life Science, Kindai University.
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.
Insights
Nervonic acid (NA) shows promise as a novel therapeutic for triple-negative breast cancer (TNBC). NA reduced cancer cell viability, inhibited growth and metastasis in mice, and induced apoptosis, suggesting potential as a new TNBC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies, necessitating novel treatment strategies.
- Fatty acids exhibit complex roles in cancer, with potential for both inhibition and promotion.
- The anti-cancer effects of nervonic acid (NA), a monounsaturated fatty acid, remain largely unexplored.
Purpose of the Study:
- To investigate the anti-cancer effects of nervonic acid (NA) on triple-negative breast cancer (TNBC).
- To evaluate NA's impact on TNBC cell viability, apoptosis, proliferation, migration, and invasion.
- To assess NA's efficacy in reducing tumor growth and metastasis in a preclinical TNBC mouse model.
Main Methods:
- In vitro: BT-549 TNBC cells were treated with varying concentrations of NA.
- In vivo: Female athymic nude mice with BT-549 xenografts received NA treatment.
- Assays included cell viability, apoptosis markers (single-stranded DNA), proliferation marker (Ki-67), apoptosis inhibitor (NF-κB), cell migration/invasion assays, and tumor growth/metastasis monitoring.
Main Results:
- NA significantly reduced BT-549 cell viability in a dose-dependent manner.
- NA induced apoptosis, inhibited proliferation, and suppressed cell migration and invasion in vitro.
- NA treatment significantly decreased tumor growth and lung metastasis in vivo.
- NA modulated key molecular markers including NF-κB, Ki-67, E-cadherin, N-cadherin, and MMPs.
Conclusions:
- Nervonic acid demonstrates significant antitumor activity against triple-negative breast cancer.
- NA exhibits potential as a novel therapeutic agent for TNBC, warranting further clinical investigation.
- The findings support NA's role in inhibiting TNBC progression through apoptosis induction and anti-metastatic effects.
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