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Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines
Dissertation (MSc (Physiology))--University of Pretoria, 2020.
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| Language: | English |
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University of Pretoria
2023
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| _version_ | 1867613484964904960 |
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| access_status_str | Open Access |
| author2 | Visagie, M.H. (Michelle Helen) |
| author_browse | Visagie, M.H. (Michelle Helen) |
| author_facet | Visagie, M.H. (Michelle Helen) |
| collection | Thesis |
| dc_rights_str_mv | © 2021 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 (Physiology))--University of Pretoria, 2020. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/93174 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:36:53.259Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2023 |
| publishDateRange | 2023 |
| publishDateSort | 2023 |
| 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:2263/93174 Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines Visagie, M.H. (Michelle Helen) tebogo_lebelo@yahoo.com Joubert, Annie M. Lebelo, Maphuti Tebogo UCTD ESE-one Non-sulphamoylated Sulphamoylated Antiproliferation Health sciences theses SDG-03 Health sciences theses SDG-17 Dissertation (MSc (Physiology))--University of Pretoria, 2020. 2-Methoxyestradiol (2ME), a 17β-estradiol metabolite, exerts anticancer properties however, the compound was found to possess low bioavailability. This resulted in the in silico-design of 2ME analogues with a sulphamoyl moiety which made them more potent than the parent compound. Sulphamoylated 2ME analogues are suspected to induce the antitumourigenic effects through the induction of reactive oxygen species. However, the exact role of oxidative stress in the activity exerted by these compounds remains elusive. In the current study, 2-ethyl-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17- decahydro-6-cyclopenta[a]phenanthrane-3 sulphamate (ESE-one) was chosen as a sulphamoylated estradiol analogue representative to investigate the role of reactive oxygen species (ROS) in the effects exerted by these sulphamoylated compounds on cell proliferation, morphology, cell cycle progression, antioxidant activity and mitochondrial membrane potential in estrogen receptor positive breast epithelial adenocarcinoma (MCF-7) cells and estrogen receptor negative breast epithelial adenocarcinoma (MDA-MB-231) cells. Fluorescent microscopy data revealed that sulphamoylated estradiol analogues induced more ROS production compared to their non-sulphamoylated counterparts in both MCF-7- and MDA-MB-231 cells. Crystal violet staining demonstrated a significant growth inhibition in cells exposed to sulphamoylated estradiol analogues compared to cells exposed to the non-sulphamoylated compounds. ESE-one exposure resulted in a ROS-dependent growth inhibition which was repressed by tiron (superoxide inhibitor), trolox (peroxyl inhibitor) and DMTU (hydrogen peroxide inhibitor). ESE-one exposure to MCF-7- and MDA-MB-231 cells resulted in an accumulation of cells in G2/M phase after 24 hours and sub-G1 phase after 48 hours. The effect induced after 24 hours exposure was inhibited by tiron and trolox, and that induced after 48 hours exposure was inhibited by tiron, trolox and DMTU. Proliferation data was confirmed by morphology studies. Tiron, trolox and DMTU significantly decreased the number of rounded cells, shrunken cells and apoptotic bodies in MCF-7 and MDA-MB-231 cells induced by ESE-one exposure; cell density was recuperated indicating the rescue effects of ROS inhibitors. Antioxidant activity data demonstrated that ESE-one induced cell rounding and antiproliferative effects via ROS evident in the reduced catalase protein concentration in MCF-7 cells which was opposed by tiron and DMTU and in MDAMB- 231 cells, inhibited by tiron and trolox. Reduction in mitochondrial membrane potential was inhibited by tiron in MCF-7 cells and DMTU in MDA-MB-231 cells. This in vitro study suggests that ESE-one induces growth inhibition, cell rounding, cell cycle arrest, catalase inhibition and depolarization of the mitochondrial membrane by production of superoxide anion, peroxyl radical and hydrogen peroxide which culminates in apoptosis. This study contributes to targeted therapy based on ROS-dependent cell death pathways in tumourigenic breast cells. em2026 Physiology MSc (Physiology) Unrestricted SDG-03: Good health and well-being SDG-17: Partnerships for the goals 2023-11-07T08:20:51Z 2023-11-07T08:20:51Z 2020-04 2020 Dissertation * A2020 http://hdl.handle.net/2263/93174 en © 2021 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 ESE-one Non-sulphamoylated Sulphamoylated Antiproliferation Health sciences theses SDG-03 Health sciences theses SDG-17 Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines |
| title | Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines |
| title_full | Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines |
| title_fullStr | Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines |
| title_full_unstemmed | Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines |
| title_short | Investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines |
| title_sort | investigating the role of oxidative stress in apoptosis induced by a sulphamoylated estradiol analogue in breast cell lines |
| topic | UCTD ESE-one Non-sulphamoylated Sulphamoylated Antiproliferation Health sciences theses SDG-03 Health sciences theses SDG-17 |
| url | http://hdl.handle.net/2263/93174 |