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.
