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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

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EA2160 Mer Molécules Santé, Le Mans Université, F-72085 Le Mans, France
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CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Université de Nantes, F-44000 Nantes, France
3
CRCINA, INSERM, Université d’Angers, Université de Nantes, F-44000 Nantes, France
*
Author to whom correspondence should be addressed.
Int. J. Environ. Res. Public Health 2020, 17(10), 3746; https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph17103746
Received: 11 April 2020 / Revised: 20 May 2020 / Accepted: 22 May 2020 / Published: 25 May 2020
(This article belongs to the Special Issue Feature Papers in Women's Health)
Despite considerable efforts in prevention and therapy, breast cancer remains a major public health concern worldwide. Numerous studies using breast cancer cell lines have shown the antiproliferative and pro-apoptotic effects of docosahexaenoic acid (DHA). Some studies have also demonstrated the inhibitory effect of DHA on the migration and invasion of breast cancer cells, making DHA a potential anti-metastatic agent. Thus, DHA has shown its potential as a chemotherapeutic adjuvant. However, the molecular mechanisms triggering DHA effects remain unclear, and the aim of this study was to provide a transcriptomic basis for further cellular and molecular investigations. Therefore, MDA-MB-231 cells were treated with 100 µM DHA for 12 h or 24 h before RNA-seq analysis. The results show the great impact of DHA-treatment on the transcriptome, especially after 24 h of treatment. The impact of DHA is particularly visible in genes involved in the cholesterol biosynthesis pathway that is strongly downregulated, and the endoplasmic reticulum (ER)-stress response that is, conversely, upregulated. This ER-stress and unfolded protein response could explain the pro-apoptotic effect of DHA. The expression of genes related to migration and invasion (especially SERPINE1, PLAT, and MMP11) is also impacted by DHA. In conclusion, this transcriptomic analysis supports the antiproliferative, pro-apoptotic and anti-invasive effects of DHA, and provides new avenues for understanding its molecular mechanisms. View Full-Text
Keywords: apoptosis; breast cancer; cholesterol metabolism; docosahexaenoic acid; ER-stress; migration; invasion; lipid metabolism; unfolded protein response apoptosis; breast cancer; cholesterol metabolism; docosahexaenoic acid; ER-stress; migration; invasion; lipid metabolism; unfolded protein response
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MDPI and ACS Style

Chénais, B.; Cornec, M.; Dumont, S.; Marchand, J.; Blanckaert, V. 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. Int. J. Environ. Res. Public Health 2020, 17, 3746. https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph17103746

AMA Style

Chénais B, Cornec M, Dumont S, Marchand J, Blanckaert V. 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. 2020; 17(10):3746. https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph17103746

Chicago/Turabian Style

Chénais, Benoît, Marine Cornec, Solenne Dumont, Justine Marchand, and Vincent Blanckaert. 2020. "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 17, no. 10: 3746. https://0-doi-org.brum.beds.ac.uk/10.3390/ijerph17103746

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