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

Benoît Chénais, Marine Cornec, Solenne Dumont, Justine Marchand and Vincent Blanckaert
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Benoît Chénais: EA2160 Mer Molécules Santé, Le Mans Université, F-72085 Le Mans, France
Marine Cornec: CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Université de Nantes, F-44000 Nantes, France
Solenne Dumont: CHU Nantes, Inserm, CNRS, SFR Santé, Inserm UMS 016, CNRS UMS 3556, Université de Nantes, F-44000 Nantes, France
Justine Marchand: EA2160 Mer Molécules Santé, Le Mans Université, F-72085 Le Mans, France
Vincent Blanckaert: EA2160 Mer Molécules Santé, Le Mans Université, F-72085 Le Mans, France

IJERPH, 2020, vol. 17, issue 10, 1-21

Abstract: 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.

Keywords: apoptosis; breast cancer; cholesterol metabolism; docosahexaenoic acid; ER-stress; migration; invasion; lipid metabolism; unfolded protein response (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2020
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