title: 17β-estradiol-containing liposomes as a novel delivery system for the antisense therapy of ER-positive breast cancer: An in vitro study on the MCF-7 cell line.
abstract: The present study suggests and describes the application of a delivery system for antisense oligonucleotides against mRNA encoding estrogen receptor proteins α and β. The delivery system is composed of a cationic liposome envelope containing 17β-estradiol (E2) in its structure. Cationic liposomes protect cargo against the extracellular matrix, and E2 can increase its shuttling efficiency into cells. Using MCF-7 cells derived from estrogen receptor-positive ductal carcinoma, treatment with liposomes against ERα was found to decrease MCF-7 proliferation, and importantly the application of both the antisense against ERα and β exhibited an antiproliferative effect expressed as cell viability. Using qRT-PCR, it was shown that MT1A, NF-κB1 and K-ras genes, but not TFF1, were downregulated using E2-based liposomes (evaluated at P=0.05). Further indicators of oxidative stress were employed to assess the effect on treatment efficiency. Glutathione (GSH/GSSG redox ratio), metallothionein (MT) and malondialdehyde (MDA) confirmed a positive effect of antisense therapy resulting in their decreased levels in the MCF-7 cells. Based on these data, we suggest that E2-based liposomes offer sufficient transfer efficiency and moreover, due to the effect on NF-κB1, MT and GSH, tumor cells can be chemosensitized to increase treatment effectiveness.
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Heger
authors.affiliation: Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic.
authors.forename: Jaromir
authors.initials: J
authors.lastname: Gumulec
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Natalia
authors.initials: N
authors.lastname: Cernei
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Tmejova
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kopel
authors.affiliation: Central European Institute of Technology, Brno University of Technology, CZ-616 00 Brno, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Balvan
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Masarik
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Ondrej
authors.initials: O
authors.lastname: Zitka
authors.affiliation: Department of Ecology and Diseases of Game, Fish and Bees, Faculty of Veterinary Hygiene and Ecology, University of Veterinary and Pharmaceutical Sciences, CZ-612 42 Brno, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Beklova
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
authors.affiliation: Department of Chemistry and Biochemistry, Mendel University in Brno, CZ-613 00 Brno, Czech Republic.
authors.forename: Rene
authors.initials: R
authors.lastname: Kizek
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D008315:Malondialdehyde / Q000737:chemistry; D008668:Metallothionein / Q000737:chemistry; D008858:Microscopy, Phase-Contrast; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D011960:Receptors, Estrogen / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011960:Receptors, Estrogen; D004958:Estradiol; D008315:Malondialdehyde; D008668:Metallothionein; D005978:Glutathione; D010100:Oxygen