Fatty Acids of CLA-Enriched Egg Yolks Can Induce Transcriptional Activation of Peroxisome Proliferator-Activated Receptors in MCF-7 Breast Cancer Cells

Abstract

In our previous study, we showed that fatty acids from CLA-enriched egg yolks (EFA-CLA) reduced the proliferation of breast cancer cells; however, the molecular mechanisms of their action remain unknown. In the current study, we used MCF-7 breast cancer cell line to determine the effect of EFA-CLA, as potential ligands for peroxisome proliferator-activated receptors (PPARs), on identified in silico PPAR-responsive genes: BCAR3, TCF20, WT1, ZNF621, and THRB (transcript TRβ2). Our results showed that EFA-CLA act as PPAR ligands with agonistic activity for all PPAR isoforms, with the highest specificity towards PPARγ. In conclusion, we propose that EFA-CLA-mediated regulation of PPAR-responsive genes is most likely facilitated by cis9,trans11CLA isomer incorporated in egg yolk. Notably, EFA-CLA activated PPAR more efficiently than nonenriched FA as well as synthetic CLA isomers. We also propose that this regulation, at least in part, can be responsible for the observed reduction in the proliferation of MCF-7 cells treated with EFA-CLA.

Pivotal Roles of Peroxisome Proliferator-Activated Receptors (PPARs) and Their Signal Cascade for Cellular and Whole-Body Energy Homeostasis

“…FAs from conjugated linoleic acid-enriched egg yolks (EFA-CLA) act as a potential ligand for PPAR receptors in the breast cancer cell line MCF-7. PPAR-responsive genes can be regulated by EFA-CLA, leading to reduced tumor cell proliferation, which has a greater influence than non-enriched FAs or single synthetic CLA isomers [ 78 ]. PPAR modulators may have beneficial effects as chemo-preventive agents.…”

Mechanisms of Anticancer Activity of a Fatty Acid Mixture Extracted from Hen Egg Yolks Enriched in Conjugated Linoleic Acid Diene (CLA) against WM793 Melanoma Cells

“…The release of cytochrome C from the mitochondrion into the cytoplasm under the influence of a mixture of FA-CLA fatty acids and synthetic isomers in their work was described by Koronowicz et.al. [19] and Miglietta et al [20], respectively.…”

“…The production process of chicken eggs biofortified in conjugated linoleic acid diene, the extraction of fatty acids, as well as their chromatographic separation and identification were described in the previous study by Koronowicz et al [ 8 ]. Briefly, to obtain CLA-enriched eggs, Isa Brown laying hens were fed a modified “DJ” mix with 0.75% CLA for 4 months.…”

Importância Do Ácido Linoleico Conjugado (Cla) Em Produtos De Origem Animal

“…Dentre estes efeitos, destaca-se a sua atividade antitumoral (BEDEL et al, 2017), já observada em diversos tecidos como o pulmão (ORALDI et al, 2013), estomacal (BAE et al, 2013), câncer de endométrio ( WANG et al, 2013), colón (PIERRE et al, 2013), prostático (SONG et al, 2006, sendo que os tumores da glândula mamária parecem ser mais sensíveis a intervenção desse composto (MAJUMDER et al, 2002;KORONOWICZ et al, 2017). Estudos evidenciam que o CLA atua sobre o crescimento e desenvolvimento tumoral em seus diversos estágios (iniciação, promoção, progressão e metástase), por meio da diminuição ou retenção da multiplicação celular, atuando ainda no aumento da morte celular programada (apoptose) e, ainda, sobre a necrose (FIELD; SCHLEY, 2004).…”