Signaling pathways of ESE-16, an antimitotic and anticarbonic anhydrase estradiol analog, in breast cancer cells

Show simple item record Stander, Barend Andre Joubert, Fourie Tu, Chingkuang Sippel, Katherine H. McKenna, Robert Joubert, Annie M. 2013-03-13T06:10:14Z 2013-03-13T06:10:14Z 2013-01-31
dc.description.abstract The aim of this study was to characterize the in vitro action of 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) on non-tumorigenic MCF-12A, tumorigenic MCF-7 and metastatic MDA-MB-231 breast cancer cells. ESE-16 is able to inhibit the activity of a carbonic anhydrase II and a mimic of carbonic anhydrase IX in the nanomolar range. Gene and protein expression studies using various techniques including gene and antibody microarrays and various flow cytometry assays yielded valuable information about the mechanism of action of ESE-16. The JNK pathway was identified as an important pathway mediating the effects of ESE-16 while the p38 stress-induced pathway is more important in MDA-MB-231 cells exposed to ESE-16. Lysosomal rupture and iron metabolism was identified as important mediators of mitochondrial membrane depolarization. Abrogation of Bcl-2 phosphorylation status as a result of ESE-16 also plays a role in inducing mitochondrial membrane depolarization. The study provides a basis for future research projects to develop the newly synthesized compound into a clinically usable anticancer agent either alone or in combination with other agents. Keywords: Antimitotic, anticarbonic anhydrase IX, apoptosis, autophagy, cell cycle arrest, Bcl-2, JNK, p38, mitochondrial membrane depolarization, flow cytometry, gene expression and protein microarray, anticancer. en_US
dc.description.librarian am2013 en_US
dc.description.librarian ay2013 en
dc.description.sponsorship This research was supported by grants from the Medical Research Council of South Africa (AG374, AK076), the Cancer Association of South Africa (AK246), National Research Foundation (NRF) (AL239), the Research Committee of the Faculty of Health Sciences (RESCOM) of University of Pretoria and the Struwig-Germeshuysen Cancer Research Trust of South Africa (AJ038, AN074). en_US
dc.description.uri en_US
dc.identifier.citation Stander BA, Joubert F, Tu C, Sippel KH, McKenna R, et al. (2013) Signaling Pathways of ESE-16, an Antimitotic and Anticarbonic Anhydrase Estradiol Analog, in Breast Cancer Cells. PLoS ONE 8(1): e53853. DOI: 10.1371/journal.pone.0053853 en_US
dc.identifier.issn 1932-6203
dc.identifier.other 10.1371/journal.pone.0053853
dc.language.iso en en_US
dc.publisher Public Library of Science en_US
dc.rights © 2013 Stander et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License en_US
dc.subject Breast cancer cells en_US
dc.subject ESE-16 en_US
dc.subject.lcsh Breast -- Cancer -- Research en
dc.subject.lcsh Antineoplastic agents en
dc.title Signaling pathways of ESE-16, an antimitotic and anticarbonic anhydrase estradiol analog, in breast cancer cells en_US
dc.type Article en_US

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