Abstract:
2-Methoxyestradiol (2ME), a 17β-estradiol metabolite, exerts anticancer properties
in vitro and in vivo. To address 2ME’s low bioavailability, research led to the in silico design
of sulphamoylated 2ME analogues. However, the role of oxidative stress induced in the activity
exerted by sulphamoylated compounds remains elusive. In the current study, the influence of
2-Ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulphamate (ESE-one) on reactive oxygen species (ROS)
induction and its effect on cell proliferation, as well as morphology, were assessed in breast tumorigenic
cells (MCF-7 and MDA-MB-231). Fluorescent microscopy showed that sulphamoylated estradiol
analogues induced hydrogen peroxide and superoxide anion, correlating with decreased cell growth
demonstrated by spectrophotometry data. ESE-one exposure resulted in antiproliferation which
was repressed by tiron (superoxide inhibitor), trolox (peroxyl inhibitor) and N,N0
-dimethylthiourea
(DMTU) (hydrogen peroxide inhibitor). Morphological studies demonstrated that tiron, trolox and
DMTU significantly decreased the number of rounded cells and shrunken cells in MCF-7 and
MDA-MB-231 cells induced by ESE-one. This in vitro study suggests that ESE-one induces growth
inhibition and cell rounding by production of superoxide anion, peroxyl radical and hydrogen
peroxide. Identification of these biological changes in cancer cells caused by sulphamoylated
compounds hugely contributes towards improvement of anticancer strategies and the ROS-dependent
cell death pathways in tumorigenic breast cells.
