Abstract:
In the present study, the antiproliferative mechanism of action of 1 M 2-methoxyestradiol (2ME) was
investigated in the MCF-7 cell line. Measurement of intracellular cyclin B and cytochrome c protein
levels, reactive oxygen species formation, cell cycle progression and apoptosis induction were conducted
by means of flow cytometry. Morphological changes were evaluated using transmission electron
microscopy and fluorescent microscopy by employing Hoechst 33342 and acridine orange. Gene expression
changes were conducted by means of microarrays. 2ME-treated cells demonstrated an increase in
cyclin B protein levels, hydrogen peroxide formation, intracellular levels of cytochrome c, as well as an
increase in early and late stages of apoptosis. In addition, morphological data revealed the presence of
autophagic processes. Fluorescent microscopy showed an increase in acridine orange staining and electron
microscopy revealed an increase in vacuolar formation in 2ME-treated cells. The gene expression
of several genes associated with mRNA translation, autophagy-related processes and genes involved in
microtubule dynamics were affected. The study contributes to the mechanistic understanding of 2ME’s
growth inhibition in MCF-7 cells and highlights the possibility of both apoptotic and autophagic processes
being activated in response to 2ME treatment in this cell line.
