In vitro changes in mitochondrial potential, aggresome formation and caspase activity by a novel 17-β-estradiol analogue in breast adenocarcinoma cells

• Published in: Cell biochemistry and function 2013-10, Vol.31 (7), p.566-574
• Main Authors: Nkandeu, Danielle S., Mqoco, Thandi V., Visagie, Michelle H., Stander, Barend A., Wolmarans, Elize, Cronje, Marianne J., Joubert, Annie M.
• Format: Article
• Language: English
• Subjects: 2-methoxyestradiol; Adenocarcinoma; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; autophagy; Autophagy - drug effects; Breast Neoplasms; Caspase 7 - metabolism; Caspase 8 - metabolism; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrenes - pharmacology; Female; Humans; MCF-7; MCF-7 Cells; Membrane Potential, Mitochondrial - drug effects; Protein Folding; Sulfonamides - pharmacology
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.2937

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. Copyright © 2013 John Wiley & Sons, Ltd.