Abstract:
2-methoxyestradiol (2ME2) exerts estrogen receptor independent antiproliferative, antiangiogenic and antitumor
activity in vitro and in vivo. Due low bioavailability and fast metabolic degradation, several analogues have been
developed in recent years. 2-Methoxyestradiol-bis-sulphamate (2-MeOE2bisMATE) is a bis-sulphamoylated
derivative of 2ME2 with antiproliferative activity. The aim of this study was to investigate cell signaling events
exerted by 2-MeOE2bisMATE in a non-tumorigenic cell line (MCF-12A) by analysing its influence on cell number,
morphology, membrane integrity and possible induction of apoptosis and autophagy. Dose-and time-dependent
studies revealed that 48 h exposure of 2-MeOE2bisMATE (0.4μM) resulted in a decrease of cell numbers to 79%. A
slight increase in the lactate dehydrogenase production was observed in the 2-MeOE2bisMATE-treated cells.
Morphological studies revealed an increase of cells in metaphase. Hallmarks of apoptosis namely nuclear
fragmentation and apoptotic bodies were also observed. In addition, increased lysosomal staining was observed by
conducting fluorescent microscopy suggesting induction of another type of cell death namely autophagy. Since 2-
MeOE2bisMATE is regarded as a potential anti-cancer agent, it is also imperative to investigate its influence and
susceptibility on non-tumorigenic cells. Data generated from this study contributes to understanding the action
mechanism of 2-MeOE2bisMATE exerted on the non-tumorigenic MCF-12A breast epithelial cell line.
