Induction of the intrinsic apoptotic pathway via a new antimitotic agent in an esophageal carcinoma cell line

Show simple item record Wolmarans, Elize Sippel, Katherine H. McKenna, Robert Joubert, Annie M. 2015-02-17T07:18:25Z 2015-02-17T07:18:25Z 2014-11
dc.description.abstract BACKGROUND : 2-Ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) is a unique, in silico-designed compound with possible anticancer properties, which were identified in our laboratory. This compound is capable of interfering with microtubule dynamics and is believed to have potential carbonic anhydrase IX inhibiting activity. In this study, it was investigated whether ESE-16 is capable of inducing apoptosis in vitro in the esophageal carcinoma SNO cell line via the intrinsic pathway at a concentration of 0.2 μM with an exposure time of 24 hours. RESULTS : Qualitative results were obtained via light microscopy, transmission electron microscopy and confocal microscopy. Results showed hallmarks of apoptosis in the ESE-16-treated cells. In addition, data revealed an increase in the number of ESE-16-treated cells blocked in metaphase. Cell death via apoptosis in the ESE-16-treated cells was confirmed by studying the internal ultrastructure of the cells via transmission electron microscopy, while confocal microscopy revealed abnormal spindle formation and condensed chromatin in ESE-16-treated cells, thus confirming metaphase block. Quantitative results were obtained via flow cytometry and spectrophotometry. Cell death via apoptosis in ESE-16-treated cells was quantitatively confirmed by the Annexin V-FITC apoptosis detection assay. Flow cytometry and spectrophotometry revealed dissipation of mitochondrial membrane potential and an increase in superoxide levels in the ESE-16-treated cells when compared to the relevant controls. Both initiator caspase 9 and effector caspase 3 activities were increased, which demonstrates that ESE-16 causes cell death in a caspase-dependent manner. CONCLUSIONS : This was the first in vitro study conducted to investigate the action mechanism of ESE-16 on an esophageal carcinoma cell line. The results provided valuable information on the action mechanism of this potential anticancer agent. It can be concluded that the novel in silico-designed compound exerts an anti-proliferative effect on the esophageal carcinoma SNO cell line by disrupting microtubule function resulting in metaphase block. This culminates in apoptotic cell death via the intrinsic apoptotic pathway. This research provided cellular targets warranting in vivo assessment of ESE-16’s potential as an anticancer agent. en_ZA
dc.description.librarian hb2015 en_ZA
dc.description.sponsorship Medical Research Council of South Africa, the Cancer Association of South Africa, Research Committee of the University of Pretoria (RESCOM), the National Research Foundation (NRF), the Institute for Cellular and Molecular Medicine (ICMM) and the Struwig- Germeshuysen Cancer Research Trust of South Africa. en_ZA
dc.description.uri en_ZA
dc.identifier.citation Wolmarans, E, Sippel, KH, McKenna, R & Joubert, AM 2014, 'Induction of the intrinsic apoptotic pathway via a new antimitotic agent in an esophageal carcinoma cell line', Cell and Bioscience, vol. 4, art. 68, pp. 1-14. en_ZA
dc.identifier.issn 2045-3701 (print)
dc.identifier.other 10.1186/2045-3701-4-68
dc.language.iso en en_ZA
dc.publisher BioMed Central en_ZA
dc.rights © 2014 Wolmarans et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated. en_ZA
dc.subject 2-Ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene en_ZA
dc.subject Esophageal carcinoma en_ZA
dc.subject Intrinsic apoptotic pathway en_ZA
dc.title Induction of the intrinsic apoptotic pathway via a new antimitotic agent in an esophageal carcinoma cell line en_ZA
dc.type Article en_ZA

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