Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines

Recent findings revealed that 2-ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate (ESE-one) induces antiproliferative activity and cell rounding dependent on the generation of superoxide anion, hydrogen peroxide and peroxyl radical. In the current study, the role of these reactive oxygen species was...

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Main Authors: Maphuti T. Lebelo, Anna M. Joubert, Michelle H. Visagie
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/3/622
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spelling doaj-ba36a24dd24a488aac2d2d825ce4bf562021-01-26T00:06:16ZengMDPI AGMolecules1420-30492021-01-012662262210.3390/molecules26030622Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell LinesMaphuti T. Lebelo0Anna M. Joubert1Michelle H. Visagie2Department of Physiology, University of Pretoria, Private Bag X323, Gezina, Pretoria 0031, South AfricaDepartment of Physiology, University of Pretoria, Private Bag X323, Gezina, Pretoria 0031, South AfricaDepartment of Physiology, University of Pretoria, Private Bag X323, Gezina, Pretoria 0031, South AfricaRecent findings revealed that 2-ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate (ESE-one) induces antiproliferative activity and cell rounding dependent on the generation of superoxide anion, hydrogen peroxide and peroxyl radical. In the current study, the role of these reactive oxygen species was assessed in the activity exerted by ESE-one on cell cycle progression, mitochondrial membrane potential and cell death induction in breast tumorigenic cells. The influence of ESE-one was also investigated on superoxide dismutase and catalase activity. ESE-one induced a time-dependent accumulation of cells in the G<sub>1</sub> phase and G<sub>2</sub>/M phase that is partially impaired by tiron and trolox and <i>N</i>,<i>N</i>′-dimethylthiourea suggesting that superoxide anion, hydrogen peroxide and peroxyl radical are required for these effects exerted by ESE-one. Flow cytometry data in MCF-7 cells demonstrated that tiron decreased depolarization of the membrane potential in ESE-one exposed cells, indicating that superoxide anion plays a role in the depolarization effects induced by ESE-one. Spectrophotometry data showed that ESE-one decreased catalase activity in both cell lines. This study contributes towards pertinent information regarding the effects of an in silico-designed sulfamoylated compound on antioxidant enzymes leading to aberrant quantities of specific reactive oxygen species resulting in antimitotic activity culminating in the induction of cell death in breast cancer cell lines.https://www.mdpi.com/1420-3049/26/3/622ESE-onesuperoxide dismutasecatalasecell cycle progressionmitochondrial membrane depolarization
collection DOAJ
language English
format Article
sources DOAJ
author Maphuti T. Lebelo
Anna M. Joubert
Michelle H. Visagie
spellingShingle Maphuti T. Lebelo
Anna M. Joubert
Michelle H. Visagie
Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines
Molecules
ESE-one
superoxide dismutase
catalase
cell cycle progression
mitochondrial membrane depolarization
author_facet Maphuti T. Lebelo
Anna M. Joubert
Michelle H. Visagie
author_sort Maphuti T. Lebelo
title Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines
title_short Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines
title_full Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines
title_fullStr Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines
title_full_unstemmed Dysregulation of Catalase by a Sulphamoylated Estradiol Analogue Culminates in Antimitotic Activity and Cell Death Induction in Breast Cancer Cell Lines
title_sort dysregulation of catalase by a sulphamoylated estradiol analogue culminates in antimitotic activity and cell death induction in breast cancer cell lines
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-01-01
description Recent findings revealed that 2-ethyl-17-oxoestra-1,3,5(10)-trien-3-yl sulfamate (ESE-one) induces antiproliferative activity and cell rounding dependent on the generation of superoxide anion, hydrogen peroxide and peroxyl radical. In the current study, the role of these reactive oxygen species was assessed in the activity exerted by ESE-one on cell cycle progression, mitochondrial membrane potential and cell death induction in breast tumorigenic cells. The influence of ESE-one was also investigated on superoxide dismutase and catalase activity. ESE-one induced a time-dependent accumulation of cells in the G<sub>1</sub> phase and G<sub>2</sub>/M phase that is partially impaired by tiron and trolox and <i>N</i>,<i>N</i>′-dimethylthiourea suggesting that superoxide anion, hydrogen peroxide and peroxyl radical are required for these effects exerted by ESE-one. Flow cytometry data in MCF-7 cells demonstrated that tiron decreased depolarization of the membrane potential in ESE-one exposed cells, indicating that superoxide anion plays a role in the depolarization effects induced by ESE-one. Spectrophotometry data showed that ESE-one decreased catalase activity in both cell lines. This study contributes towards pertinent information regarding the effects of an in silico-designed sulfamoylated compound on antioxidant enzymes leading to aberrant quantities of specific reactive oxygen species resulting in antimitotic activity culminating in the induction of cell death in breast cancer cell lines.
topic ESE-one
superoxide dismutase
catalase
cell cycle progression
mitochondrial membrane depolarization
url https://www.mdpi.com/1420-3049/26/3/622
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AT annamjoubert dysregulationofcatalasebyasulphamoylatedestradiolanalogueculminatesinantimitoticactivityandcelldeathinductioninbreastcancercelllines
AT michellehvisagie dysregulationofcatalasebyasulphamoylatedestradiolanalogueculminatesinantimitoticactivityandcelldeathinductioninbreastcancercelllines
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