Abstract:
In anticancer research where the focus is on
finding agents that induces cell death while leaving nontumorigenic
cells less affected, a novel 2-methoxyestradiol
derivative has come forth. 2-Methoxyestradiol-bis-sulfamate
(2-MeOE2bisMATE) is a 2-methoxyestradiol derivative
produced by bis-sulphamoylation, which possesses increased
antiproliferative activity and biological availability. Several
questions remain regarding the type of cell death mechanisms
and possible induction of autophagy by 2-MeOE2bisMATE.
The aim of this in vitro study was to investigate the cell death
mechanisms exerted by 2-MeOE2bisMATE in an adenocarcinoma
cell line (MCF-7) by analyzing its influence on cell
growth, morphology, and possible induction of cell death.
Spectrophotometry (crystal violet staining), transmission
electron microscopy (TEM), light microscopy (hematoxylin
and eosin staining), and fluorescent microscopy (Hoechst
33342, propidium iodide and acridine orange) were
employed. Spectrophotometrical studies indicated that
2-MeOE2bisMATE decreased cell numbers to 75% inMCF-
7 cells after 24 h and to 47% after 48 h of exposure. TEM
demonstrated membrane blebbing, nuclear fragmentation,
and chromatin condensation indicating the hallmarks of
apoptosis. Light microscopy revealed the presence of several
cells blocked in metaphase, and apoptotic cells were also
observed. Fluorescent microscopy demonstrated increased
lysosomal staining; suggesting the induction of autophagy.
2-MeOE2bisMATE shows therapeutic potential, as an, anticancer agent, and the investigation of the cell death
mechanisms used by 2-MeOE2bisMATE, thus, warrants
further investigation.
