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

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Authors

Nkandeu, Danielle Sandra
Mqoco, Thandi Vuyelwa
Visagie, Michelle Helen
Stander, Barend Andre
Wolmarans, Elize
Cronje, Marianne J.
Joubert, Annie M.

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Publisher

Wiley

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-b-estradiol analogue, was tested on the breast adenocarcinoma MCF-7 cell line. The in vitro influence of 24 h exposure to 0.18 mM 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.

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Keywords

2-Methoxyestradiol (2ME2), MCF-7, Autophagy, Apoptosis

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Citation

Nkandeu, DS, Mqoco, TV, Visagie, MH, Stander, BA, Wolmarans, E, Cronje, MJ & Joubert, AM 2013, 'In vitro changes in mitochondrial potential, aggresome formation and caspase activity by a novel 17-beta-estradiol analogue in breast adenocarcinoma cells', Cell Biochemistry and Function, vol. 31, no. 7, pp. 566-574.