title: In vitro changes in mitochondrial potential, aggresome formation and caspase activity by a novel 17-β-estradiol analogue in breast adenocarcinoma cells.
abstract: 2-Methoxyestradiol, a natural metabolite of estradiol, exerts antiproliferative and antitumour properties in vitro and in vivo. Because of its low oral bioavailability, several promising analogues of 2-methoxyestradiol have been developed. In this study, the in vitro influence of the compound, 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (C19), a non-commercially available 17-β-estradiol analogue, was tested on the breast adenocarcinoma MCF-7 cell line. The in vitro influence of 24 h exposure to 0.18 μM of C19 on MCF-7 cells was evaluated on cell morphology, cell cycle progression and possible induction of apoptosis and autophagy. Polarization-optical transmitted light differential interference contrast and fluorescence microscopy revealed the presence of cells blocked in metaphase, occurrence of apoptotic bodies and compromised cell density in C19-treated cells. Hallmarks of autophagy, namely an increase in the number of acidic vacuoles and lysosomes, were also observed in C19-treated samples. An increase in the number of cells present in the sub-G1 fraction, as well as a reduction in mitochondrial membrane potential was observed. No significant alterations in caspase 8 activity were observed. A twofold increase in aggresome formation was observed in C19-treated cells. C19 induced both apoptosis and autophagy in MCF-7 cells.
authors: Department of Physiology, University of Pretoria, South Africa.
authors: Danielle S
authors: DS
authors: Nkandeu
authors: Thandi V
authors: TV
authors: Mqoco
authors: Michelle H
authors: MH
authors: Visagie
authors: Barend A
authors: BA
authors: Stander
authors: Elize
authors: E
authors: Wolmarans
authors: Marianne J
authors: MJ
authors: Cronje
authors: Annie M
authors: AM
authors: Joubert
mesh_terms: D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001943:Breast Neoplasms; D053179:Caspase 7 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D017510:Protein Folding; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: C588027:2-ethyl-3-O-sulfamoylestra-1,3,5(10)16-tetraene; D000970:Antineoplastic Agents; D004963:Estrenes; D013449:Sulfonamides; D004958:Estradiol; D053179:Caspase 7; D053181:Caspase 8
keywords: 2-methoxyestradiol; MCF-7; apoptosis; autophagy