ArticleLipids in health and disease2015
α-linolenic acid and docosahexaenoic acid, alone and combined with trastuzumab, reduce HER2-overexpressing breast cancer cell growth but differentially regulate HER2 signaling pathways.
Article in Lipids in health and disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 35 citations in OpenAlex.
- Alpha-linolenic acid in cancer: a predictive fate-switch framework for tumor lipid reprogramming.Frontiers in oncology · 2026Article
- HSD17B4 methylation enhances glucose dependence of BT-474 breast cancer cells and increases lapatinib sensitivity.Breast cancer research and treatment · 2023Article
- Article
- Physiological and Pathological Considerations for the Use of Flaxseed as a Therapeutic Dietary Strategy.Reviews in cardiovascular medicine · 2023Review
- Antioxidant Protection against Trastuzumab Cardiotoxicity in Breast Cancer Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Uncovering the Mechanisms of Active Components from Toad Venom against Hepatocellular Carcinoma Using Untargeted Metabolomics.Molecules (Basel, Switzerland) · 2022Article
- Contribution of n-3 Long-Chain Polyunsaturated Fatty Acids to the Prevention of Breast Cancer Risk Factors.International journal of environmental research and public health · 2022Review
- α-Linolenic Acid Suppresses Proliferation and Invasion in Osteosarcoma Cells via Inhibiting Fatty Acid Synthase.Molecules (Basel, Switzerland) · 2022Article
- Article
- Transcriptomic Response of Breast Cancer Cells MDA-MB-231 to Docosahexaenoic Acid: Downregulation of Lipid and Cholesterol Metabolism Genes and Upregulation of Genes of the Pro-Apoptotic ER-Stress Pathway.International journal of environmental research and public health · 2020Article
- Article
- Role of docosahexaenoic acid in enhancement of docetaxel action in patient-derived breast cancer xenografts.Breast cancer research and treatment · 2019Article
- Article
- Omega-3 Polyunsaturated Fatty Acids Time-Dependently Reduce Cell Viability and Oncogenic MicroRNA-21 Expression in Estrogen Receptor-Positive Breast Cancer Cells (MCF-7).International journal of molecular sciences · 2018Article
- Review
- Alpha-linolenic acid regulates Cox2/VEGF/MAP kinase pathway and decreases the expression of HPV oncoproteins E6/E7 through restoration of p53 and Rb expression in human cervical cancer cell lines.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
- Omega-3 Fatty Acids and Cancer Cell Cytotoxicity: Implications for Multi-Targeted Cancer Therapy.Journal of clinical medicine · 2016Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDiets rich in the n-3 fatty acid alpha-linolenic acid (ALA) have been shown to reduce breast tumor growth, enhance the effectiveness of the HER2-targeted drug trastuzumab (TRAS) and reduce HER2 signaling in mouse models. It is unclear whether this is due to direct effects of ALA or due to its long-chain n-3 fatty acids metabolites including docosahexaenoic acid (DHA).
methodsThe ability of HER2-overexpressing BT-474 human breast cancer cells to convert ALA to long-chain n-3 fatty acids was determined by measurement of phospholipid fatty acids by gas chromatography following treatment with 100 μM ALA. The effects of 96 h treatment with ALA or DHA, at serum levels seen in mice (50-100 μM), alone and combined with TRAS (10 μg/ml), on BT-474 cell growth measured by trypan blue exclusion, apoptosis measured by flow cytometric analysis of Annexin-V/7-AAD stained cells (ALA and TRAS treatment only) and protein biomarkers HER2 signaling measured by western blot were determined.
resultsALA-treated BT-474 cells had higher phospholipid ALA but no increase in downstream n-3 metabolites including DHA. Both ALA and DHA reduced cell growth with and without TRAS. ALA had no effect on apoptosis. ALA and DHA showed opposite effects on Akt and MAPK phosphorylation; ALA increased and DHA decreased phosphorylation.
conclusionsTogether these data suggest that, while both ALA and its DHA metabolite can reduce HER2-overexpressing breast cancer growth with and without TRAS, they demonstrate for the first time that DHA is responsible for the effects of ALA-rich diets on HER2 signaling pathways.
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