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Omega-3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPARγ activation in MCF-7 breast cancer cells.
J Cell Physiol 2013; 228(6):1314-22JC

Abstract

The omega-3 long chain polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), elicit anti-proliferative effects in cancer cell lines and in animal models. Dietary DHA and EPA can be converted to their ethanolamide derivatives, docosahexaenoyl ethanolamine (DHEA), and eicosapentaenoyl ethanolamine (EPEA), respectively; however, few studies are reported on their anti-cancer activities. Here, we demonstrated that DHEA and EPEA were able to reduce cell viability in MCF-7 breast cancer cells whereas they did not elicit any effects in MCF-10A non-tumorigenic breast epithelial cells. Since DHA and EPA are ligands of peroxisome proliferator-activated receptor gamma (PPARγ), we sought to determine whether PPARγ may also mediate DHEA and EPEA actions. In MCF-7 cells, both compounds enhanced PPARγ expression, stimulated a PPAR response element-dependent transcription as confirmed by the increased expression of its target gene PTEN, resulting in the inhibition of AKT-mTOR pathways. Besides, DHEA and EPEA treatment induced phosphorylation of Bcl-2 promoting its dissociation from beclin-1 which resulted in autophagy induction. We also observed an increase of beclin-1 and microtubule-associated protein 1 light chain 3 expression along with an enhanced autophagosomes formation as revealed by mono-dansyl-cadaverine staining. Finally, we demonstrated the involvement of PPARγ in DHEA- and EPEA-induced autophagy by using siRNA technology and a selective inhibitor. In summary, our data show that the two omega-3 ethanolamides exert anti-proliferative effects by inducing autophagy in breast cancer cells highlighting their potential use as breast cancer preventive and/or therapeutic agents.

Authors+Show Affiliations

Department of Pharmaco-Biology, University of Calabria, Arcavacata di Rende (CS), Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23168911

Citation

Rovito, Daniela, et al. "Omega-3 PUFA Ethanolamides DHEA and EPEA Induce Autophagy Through PPARγ Activation in MCF-7 Breast Cancer Cells." Journal of Cellular Physiology, vol. 228, no. 6, 2013, pp. 1314-22.
Rovito D, Giordano C, Vizza D, et al. Omega-3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPARγ activation in MCF-7 breast cancer cells. J Cell Physiol. 2013;228(6):1314-22.
Rovito, D., Giordano, C., Vizza, D., Plastina, P., Barone, I., Casaburi, I., ... Andò, S. (2013). Omega-3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPARγ activation in MCF-7 breast cancer cells. Journal of Cellular Physiology, 228(6), pp. 1314-22. doi:10.1002/jcp.24288.
Rovito D, et al. Omega-3 PUFA Ethanolamides DHEA and EPEA Induce Autophagy Through PPARγ Activation in MCF-7 Breast Cancer Cells. J Cell Physiol. 2013;228(6):1314-22. PubMed PMID: 23168911.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Omega-3 PUFA ethanolamides DHEA and EPEA induce autophagy through PPARγ activation in MCF-7 breast cancer cells. AU - Rovito,Daniela, AU - Giordano,Cinzia, AU - Vizza,Donatella, AU - Plastina,Pierluigi, AU - Barone,Ines, AU - Casaburi,Ivan, AU - Lanzino,Marilena, AU - De Amicis,Francesca, AU - Sisci,Diego, AU - Mauro,Loredana, AU - Aquila,Saveria, AU - Catalano,Stefania, AU - Bonofiglio,Daniela, AU - Andò,Sebastiano, PY - 2012/10/18/received PY - 2012/11/08/accepted PY - 2012/11/22/entrez PY - 2012/11/22/pubmed PY - 2013/4/20/medline SP - 1314 EP - 22 JF - Journal of cellular physiology JO - J. Cell. Physiol. VL - 228 IS - 6 N2 - The omega-3 long chain polyunsaturated fatty acids, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), elicit anti-proliferative effects in cancer cell lines and in animal models. Dietary DHA and EPA can be converted to their ethanolamide derivatives, docosahexaenoyl ethanolamine (DHEA), and eicosapentaenoyl ethanolamine (EPEA), respectively; however, few studies are reported on their anti-cancer activities. Here, we demonstrated that DHEA and EPEA were able to reduce cell viability in MCF-7 breast cancer cells whereas they did not elicit any effects in MCF-10A non-tumorigenic breast epithelial cells. Since DHA and EPA are ligands of peroxisome proliferator-activated receptor gamma (PPARγ), we sought to determine whether PPARγ may also mediate DHEA and EPEA actions. In MCF-7 cells, both compounds enhanced PPARγ expression, stimulated a PPAR response element-dependent transcription as confirmed by the increased expression of its target gene PTEN, resulting in the inhibition of AKT-mTOR pathways. Besides, DHEA and EPEA treatment induced phosphorylation of Bcl-2 promoting its dissociation from beclin-1 which resulted in autophagy induction. We also observed an increase of beclin-1 and microtubule-associated protein 1 light chain 3 expression along with an enhanced autophagosomes formation as revealed by mono-dansyl-cadaverine staining. Finally, we demonstrated the involvement of PPARγ in DHEA- and EPEA-induced autophagy by using siRNA technology and a selective inhibitor. In summary, our data show that the two omega-3 ethanolamides exert anti-proliferative effects by inducing autophagy in breast cancer cells highlighting their potential use as breast cancer preventive and/or therapeutic agents. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/23168911/Omega_3_PUFA_ethanolamides_DHEA_and_EPEA_induce_autophagy_through_PPARγ_activation_in_MCF_7_breast_cancer_cells_ L2 - https://doi.org/10.1002/jcp.24288 DB - PRIME DP - Unbound Medicine ER -