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

• Published in: International journal of environmental research and public health 2020-05, Vol.17 (10), p.3746
• Main Authors: Chénais, Benoît, Cornec, Marine, Dumont, Solenne, Marchand, Justine, Blanckaert, Vincent
• Format: Article
• Language: English
• Subjects: Apoptosis; Biochemistry, Molecular Biology; Biosynthesis; Breast cancer; Cell cycle; Cholesterol; Docosahexaenoic acid; Endoplasmic reticulum; Fatty acids; Gene expression; Genes; Genomes; Genomics; Invasiveness; Kinases; Life Sciences; Lipid metabolism; Lipids; Metastases; Metastasis; Molecular modelling; Protein folding; Public health; Transgenic animals; Tumor cell lines
• ISSN: 1660-4601; 1661-7827; 1660-4601
• DOI: 10.3390/ijerph17103746

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 1`2 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 , , and ) 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.