Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved ora...

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Autores principales:	Michelle Visagie, Anne Theron, Thandi Mqoco, Warren Vieira, Renaud Prudent, Anne Martinez, Laurence Lafanechère, Annie Joubert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0d4768f1db5c42ceaeca946fa5dc627b
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spelling	oai:doaj.org-article:0d4768f1db5c42ceaeca946fa5dc627b2021-11-18T08:56:48ZSulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.1932-620310.1371/journal.pone.0071935https://doaj.org/article/0d4768f1db5c42ceaeca946fa5dc627b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24039728/?tool=EBIhttps://doaj.org/toc/1932-62032-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.Michelle VisagieAnne TheronThandi MqocoWarren VieiraRenaud PrudentAnne MartinezLaurence LafanechèreAnnie JoubertPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e71935 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michelle Visagie Anne Theron Thandi Mqoco Warren Vieira Renaud Prudent Anne Martinez Laurence Lafanechère Annie Joubert Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.
description	2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1-25 μM) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues.
format	article
author	Michelle Visagie Anne Theron Thandi Mqoco Warren Vieira Renaud Prudent Anne Martinez Laurence Lafanechère Annie Joubert
author_facet	Michelle Visagie Anne Theron Thandi Mqoco Warren Vieira Renaud Prudent Anne Martinez Laurence Lafanechère Annie Joubert
author_sort	Michelle Visagie
title	Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.
title_short	Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.
title_full	Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.
title_fullStr	Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.
title_full_unstemmed	Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.
title_sort	sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0d4768f1db5c42ceaeca946fa5dc627b
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Sulphamoylated 2-methoxyestradiol analogues induce apoptosis in adenocarcinoma cell lines.

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