Novel estradiol analogue induces apoptosis and autophagy in esophageal carcinoma cells

Abstract

Abstract:Cancer is the second leading cause of death in South Africa. The critical role that microtubules play in cell division makes them an ideal target for the development of chemotherapeutic drugs that prevent the hyperproliferation of cancer cells. The new in silico-designed estradiol analogue 2-ethyl-3-Osulfamoyl-estra-1,3,5(10)16-tetraene (ESE-16) was investigated in terms of its in vitro antiproliferative effects on the esophageal carcinoma SNO cell line at a concentration of 0.18 µM and an exposure time of 24 h. Polarization-optical differential interference contrast and triple fluorescent staining (propidium iodide, Hoechst 33342 and acridine orange) revealed a decrease in cell density, metaphase arrest, and the occurrence of apoptotic bodies in the ESE-16-treated cells when compared to relevant controls. Treated cells also showed an increase in the presence of acidic vacuoles and lysosomes, suggesting the occurrence of autophagic processes. Cell death via autophagy was confirmed using the Cyto- . In addition, a reduction in mitochondrial membrane potential was also observed, which suggests the involvement of apoptotic cell death induced by ESE-16 via the intrinsic apoptotic pathway. In this study, it was demonstrated that ESE-16 induces cell death via both autophagy and apoptosis in esophageal carcinoma cells. This study paves the way for future investigation into the role of ESE-16 in ex vivo and in vivo studies as a possible anticancer agent.

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

“…This observation is supported by a study where 17β estradiol analog-treated MDA-MB-231, MCF-7 and MCF-12A cells demonstrated the presence of apoptotic bodies and vacuoles [63]. Fragmented nuclei and apoptotic bodies were detected within tumorigenic cells that were exposed to combination compounds, which indicate late stages of apoptosis and also support previous cell cycle- and apoptotic quantification [28,62]. …”

“…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.…”

A Novel 2-Methoxyestradiol Analogue Is Responsible for Vesicle Disruption and Lysosome Aggregation in Breast Cancer Cells

“…Previous studies suggested that ESE-16 exposure in certain cancer cell lines leads to increased autophagy [2, 9, 10]. This conclusion was drawn from MDC staining of cells and autophagy-regulating protease 4A (Atg 4A) expression levels (Fig.…”

“…Here, we set out to obtain conclusive data to allow us to identify the origin of the vesicles formed after ESE-16 exposure. First, we compared vesicle size and distribution using MDC staining between cells exposed to ESE-16 and cells exposed to the known autophagy inducer tamoxifen [9, 10]. Our data shows that tamoxifen does indeed induce the propagation of distinct, bright MDC-positive foci.…”

Estrogen O-sulfamates and their analogues: Clinical steroid sulfatase inhibitors with broad potential

“…However, to the best of our knowledge this has not been further developed. Another generally related sulfamoylated steroid derived from this background work, ESE-16, has been more recently proposed [51] and shown to cause both apoptotic and autophagic cell death [52].…”