Omega‐3 fatty acids modulate the lipid profile, membrane architecture, and gene expression of leiomyoma cells

• Published in: Journal of cellular physiology Vol. 233; no. 9; pp. 7143 - 7156
• Main Authors: Islam, Md Soriful, Castellucci, Clara, Fiorini, Rosamaria, Greco, Stefania, Gagliardi, Riccardo, Zannotti, Alessandro, Giannubilo, Stefano R., Ciavattini, Andrea, Frega, Natale G., Pacetti, Deborah, Ciarmela, Pasquapina
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-09-2018
• Subjects: ABCA1 protein; ABCG1 and ABCA1; Activin; Arachidonic acid; Architecture; ATP-binding protein; Calcium channels (voltage-gated); Cell membranes; Collagen; Docosahexaenoic acid; Eicosapentaenoic acid; Extracellular matrix; Fatty acids; Fibroids; Fibronectin; Fluidity; Gene expression; Health services; Linoleic acid; lipid profile; Lipids; mechanical signaling; Medical treatment; Membrane fluidity; Membranes; Mitochondria; Molecular chains; Myometrium; omega‐3 fatty acids; Polyunsaturated fatty acids; Signaling; Tumors; uterine leiomyoma; Uterus; Versican; ABCG1 and ABCA1; mechanical signaling; omega-3 fatty acids; uterine leiomyoma; lipid profile
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.26537

Uterine leiomyomas (fibroids or myomas) are the most common benign tumors of premenopausal women and new medical treatments are needed. This study aimed to determine the effects of omega‐3 fatty acids on the lipid profile, membrane architecture and gene expression patterns of extracellular matrix components (collagen1A1, fibronectin, versican, or activin A), mechanical signaling (integrin β1, FAK, and AKAP13), sterol regulatory molecules (ABCG1, ABCA1, CAV1, and SREBF2), and mitochondrial enzyme (CYP11A1) in myometrial and leiomyoma cells. Myometrial tissues had a higher amount of arachidonic acid than leiomyoma tissues while leiomyoma tissues had a higher level of linoleic acid than myometrial tissues. Treatment of primary myometrial and leiomyoma cells with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) reduced the monounsaturated fatty acid (MUFA) content and increased the polyunsaturated fatty acid (PUFA) content in both cell types. Myometrial and leiomyoma cell membranes were in the liquid‐crystalline phase, but EPA‐ and DHA‐treated cells had decreased membrane fluidity. While we found no changes in the mRNA expression of ECM components, EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega‐3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.
Myometrial and leiomyoma cell membranes were in the liquid‐crystalline phase, but EPA‐ and DHA‐treated cells had decreased membrane fluidity. EPA and DHA treatment reduced levels of ABCG1, ABCA1, and AKAP13 in both cell types. EPA and DHA also reduced FAK and CYP11A1 expression in myometrial cells. The ability of omega‐3 fatty acids to remodel membrane architecture and downregulate the expression of genes involved in mechanical signaling and lipid accumulation in leiomyoma cells offers to further investigate this compound as preventive and/or therapeutic option.