Sulphamoylated estradiol analogue induces antiproliferative activity and apoptosis in breast cell lines

Abstract

Abstract:Research into potential anticancer agents has shown that 2-methoxyestradiol exerts antiproliferative activity in vitro and in vivo in an estrogen receptor-independent manner. Due to its limited biological accessibility and rapid metabolic degradation, several new analogues have been developed in recent years. This study investigated the in vitro effects of a novel in silicodesigned compound (C16) in an estrogen receptor-positive breast adenocarcinoma epithelial cell line (MCF-7), an estrogen receptor-negative breast adenocarcinoma epithelial cell line (MDA-MB-231) and a nontumorigenic breast cell line (MCF-12A). Light microscopy revealed decreased cell density, cells blocked in metaphase and the presence of apoptotic characteristics in all three cell lines after exposure to C16 for 24 h. Polarizationoptical transmitted light differential interference contrast revealed the presence of several rounded cells and decreased cell density. The xCELLigence real-time label-independent approach revealed that C16 exerted antiproliferative activity. Significant inhibition of cell growth was demonstrated after 24 h of exposure to 0.2 μM C16 in all three cell lines. However, the non-tumorigenic MCF-12A cell line recovered extremely well after 48 h when compared to the tumorigenic cell lines. This indicates that C16 acts as an antiproliferative agent, possesses antimitotic activity and induces apoptosis in vitro. These features warrant further investigation.

Synergistic Anticancer Potential of Dichloroacetate and Estradiol Analogue Exerting their Effect via ROS-JNK-Bcl-2-Mediated Signalling Pathways

“…Cells that divided in the presence of the C9+DCA treatment proceeded from being arrested at the mitotic phase to forming multiple micronuclei and apoptotic bodies. Other studies recently conducted also showed similar results where a sulphamoylated antimitotic compound-treated MCF-7, and/or MDA-MB-231 or esophageal carcinoma cells (SNO) cells showed a decrease in cell density along with morphological indicators of apoptosis [8,28,62]. Distorted cell shape, high density of digit-like apical microvilli, formations of vacuoles, lysosomes and apoptotic bodies, heterochromatin, as well as fragmented DNA were detected in both cell lines by means of transmission electron microscopy.…”

“…Haematoxylin and eosin (H&E) stains were used to recognise various cytoplasmic and nuclear morphologic changes [27], as well as to determine the mitotic index [28]. MCF-7 and MCF-12A cells were seeded in 6-well plates at a density of 375 000 cells/3 ml medium/well on heat-sterilized cover slips.…”

Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells

“…PlasDIC is an improved polarization-optical transmitted light differential interference contrast method that allows linearly polarized light to be generated only after the objective [12,31,34]. PlasDIC provides high-quality imaging of cells in plastic cell culture vessels.…”

“…2-methoxyoestradiol (2ME) is an endogenous metabolite derived from 17β-estradiol (Fig. 1A) [7][8][9][10][11][12]. Research has shown that this compound has antiproliferative, antiangiogenic and pro-apoptotic characteristics in vitro and in vivo [3,[7][8][9][12][13][14][15].…”

“…1A) [7][8][9][10][11][12]. Research has shown that this compound has antiproliferative, antiangiogenic and pro-apoptotic characteristics in vitro and in vivo [3,[7][8][9][12][13][14][15]. 2ME causes abnormal mitotic spindle formation and mitotic accumulation in estrogen receptor-positive and -negative cells [9,10,[13][14][15][16].…”