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In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line
Dissertation (MSc)--University of Pretoria, 2012.
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University of Pretoria
2013
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| _version_ | 1867613671780253696 |
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| access_status_str | Open Access |
| author2 | Joubert, Annie M. |
| author_browse | Joubert, Annie M. |
| author_facet | Joubert, Annie M. |
| collection | Thesis |
| dc_rights_str_mv | © 2012, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Dissertation (MSc)--University of Pretoria, 2012. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/31519 |
| institution | University of Pretoria (South Africa) |
| last_indexed | 2026-06-10T12:39:51.634Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2013 |
| publishDateRange | 2013 |
| publishDateSort | 2013 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/31519 In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line Joubert, Annie M. Mqoco, T.V. (Thandi Vuyelwa) UCTD Dissertation (MSc)--University of Pretoria, 2012. Oesophageal squamous cell carcinoma is one of the most frequently occurring cancers in South Africa, with its highest incidence observed in South African black males. More efficient anticancer drugs are currently being researched with the aim of discovering new compounds that will aid in the treatment of cancer. 2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite currently undergoing human clinical trials. 2ME2 exerts antitumour, antiangionenic and apoptotic effects both in vitro and in vivo. However, due to its limited bioavailability, analogues are being synthesized and tested in an attempt to improve this shortcoming. 2-Methoxyestradiol-bis-sulphamate (2-MeOE2bisMATE) is a bis-sulphamoylated derivative of 2ME2. 2-MeOE2bisMATE has antiproliferative effects both in vitro and in vivo. Although 2-MeOE2bisMATE is a potential anticancer drug the exact action mechanism of this compound is still unidentified. In this study the in vitro effects of 2-MeOE2bisMATE on cell growth, morphology, cell cycle progression, as well as its potential to induce certain types of cell death and cytotoxicity in the oesophageal carcinoma (SNO) cell line were investigated. Cell number determination studies revealed that 0.4µM of 2-MeOE2bisMATE significantly inhibited growth of SNO cells after 24 hours of exposure. Morphological studies demonstrated hallmarks of both apoptosis and autophagy such as chromatin condensation, membrane blebbing, apoptotic bodies and increased presence of autophagosomes. In addition, immunofluorescence indicated microtubule network disruption in 2-MeOE2bisMATE-treated cells when compared to vehicle-treated control cells. Fluorescent microscopy revealed that both apoptosis and autophagy were induced in SNO cells after 24 hours of exposure to 0.4µM 2-MeOE2bisMATE. Cell cycle progression analysis revealed an increase in the number of cells in the G2/M phase, as well as in the sub-G1 fraction (indicating the presence of apoptosis) of 2-MeOE2bisMATE-treated cells. The annexin V-FITC assay verified the induction of apoptosis by 2-MeOE2bisMATE. An increase in the number of cells with reduced mitochondrial membrane potential and an increased caspase 6 activity were observed in 2-MeOE2bisMATE-treated cells. Autophagy induction was confirmed by flow cytometry using cyto-ID detection and the conjugated rabbit polyclonal anti-LC3B antibody assays. This in vitro study demonstrated new insights to the action mechanism of 2-MeOE2bisMATE in oesophageal carcinoma (SNO) cells, since these activities have not been studied in oesophageal carcinoma cells up to date. Future studies are warranted to further determine which gene and protein expression changes are induced by 2-MeOE2bisMATE in SNO cells. Physiology MSc Unrestricted 2013-09-09T12:20:02Z 2012-12-14 2013-09-09T12:20:02Z 2012-09-07 2012-12-14 2012-12-13 Dissertation Mqoco, T(V 2012, In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/31519> E12/9/202/gm http://hdl.handle.net/2263/31519 http://upetd.up.ac.za/thesis/available/etd-12132012-151053/ © 2012, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line |
| title | In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line |
| title_full | In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line |
| title_fullStr | In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line |
| title_full_unstemmed | In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line |
| title_short | In vitro evaluation of 2-methoxyestradiol-bis-sulphamate on cell growth, morphology, cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma (SNO) cell line |
| title_sort | in vitro evaluation of 2 methoxyestradiol bis sulphamate on cell growth morphology cell cycle progression and its possible induction of types of cell deaths in an oesophageal carcinoma sno cell line |
| topic | UCTD |
| url | http://hdl.handle.net/2263/31519 http://upetd.up.ac.za/thesis/available/etd-12132012-151053/ |