Fatty Acids of CLA-enriched Egg Yolks Can Induce Mitochondrial Pathway of Apoptosis in MCF-7 Breast Cancer Cells

Abstract

Background: Fatty acids from conjugated linoleic acid (CLA)-enriched egg yolk suppressed the viability of the MCF-7 cancer line more effectively than non-enriched egg yolk. Herein we aimed to determine the molecular mechanisms by analysing the expression and activation of proteins involved in cellular stress and apoptosis signaling.

Materials and methods: Forty-eight Isa Brown laying hens (26-week-old) were fed a fortified (0.75% CLA) or a control diet (0% CLA) for 4 months. Collected eggs were used to obtain CLA-enriched (EFA-CLA) or non-enriched (EFA) fatty acid extracts for the treatment of the MCF-7 cancer cell line. Protein levels were analysed by PathScan® Stress and Apoptosis Signalling Antibody Array and western blot method.

Results: Treatment with EFA-CLA led to activation of caspase signalling as main effector of apoptosis. It also increased levels of pro-apoptotic B-cell lymphoma 2 family proteins as well as promoted the release of cytochrome c, second mitochondria-derived activator of caspase and mitochondrial serine protease from mitochondria to the cytoplasm. EFA-CLA increased levels of tumour protein 53 and mothers against decapentaplegic homolog 2 tumour suppressors, and activated p38 mitogen-activated protein kinases and stress-activated protein kinase/c-Jun NH2-terminal kinase proteins. Finally, treatment down-regulated anti-apoptotic extracellular signal-regulated protein kinases 1 and 2, RAC-alpha serine/threonine-protein kinase, heat-shock protein 27, inhibitor of nuclear factor κβ, transforming growth factor beta-activated kinase 1 and survivin proteins.

Conclusion: Taken together, our results suggest that activation of the mitochondrial apoptotic pathway may be a potential mechanism of EFA-CLA action.

Keywords: CLA; CLA preventive antitumour activity; CLA-enriched egg yolk; Conjugated linoleic acid; apoptosis; breast cancer; cellular stress response.