Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines

Abstract Background: Tumourigenic cells modify metabolic pathways In order to facilitate increased proliferation and cell survival resulting in glucose-and glutamine addiction. Previous research indicated that glutamine deprivation resulted in potential differential activity targeting tumourigenic...

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Autores principales:	Gwangwa,Mokgadi Violet, Joubert,Anna Margaretha, Visagie,Michelle Helen
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2019
Materias:	Glutamine deprivation ROS Mitochondrial membrane potential Cell cycle progression Apoptosis
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100213
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spelling	oai:scielo:S0716-976020190001002132019-10-10Effects of glutamine deprivation on oxidative stress and cell survival in breast cell linesGwangwa,Mokgadi VioletJoubert,Anna MargarethaVisagie,Michelle Helen Glutamine deprivation ROS Mitochondrial membrane potential Cell cycle progression Apoptosis Abstract Background: Tumourigenic cells modify metabolic pathways In order to facilitate increased proliferation and cell survival resulting in glucose-and glutamine addiction. Previous research indicated that glutamine deprivation resulted in potential differential activity targeting tumourigenic cells more prominently. This is ascribed to tumourigenic cells utilising increased glutamine quantities for enhanced glycolysis-and glutaminolysis. In this study, the effects exerted by glutamine deprivation on reactive oxygen species (ROS) production, mitochondrial membrane potential, cell proliferation and cell death in breast tumourigenic cell lines (MCF-7, MDA-MB-231, BT-20) and a non-tumourigenic breast cell line (MCF-10A) were investigated. Results: Spectrophotometry demonstrated that glutamine deprivation resulted in decreased cell growth in a time-dependent manner. MCF-7 cell growth was decreased to 61% after 96 h of glutamine deprivation; MDA-MB-231 cell growth was decreased to 78% cell growth after 96 h of glutamine deprivation, MCF-10A cell growth was decreased 89% after 96 h of glutamine deprivation and BT-20 cell growth decreased to 86% after 24 h of glutamine deprivation and remained unchanged until 96 h of glutamine deprivation. Glutamine deprivation resulted in oxidative stress where superoxide levels were significantly elevated after 96 h in the MCF-7-and MDA-MB-231 cell lines. Time-dependent production of hydrogen peroxide was accompanied by aberrant mitochondrial membrane potential. The effects of ROS and mitochondrial membrane potential were more prominently observed in the MCF-7 cell line when compared to the MDA-MB-231-, MCF-10A- and BT-20 cell lines. Cell cycle progression revealed that glutamine deprivation resulted in a significant increase in the S-phase after 72 h of glutamine deprivation in the MCF-7 cell line. Apoptosis induction resulted in a decrease in viable cells in all cell lines following glutamine deprivation. In the MCF-7 cells, 87.61% of viable cells were present after 24 h of glutamine deprivation. Conclusion: This study demonstrates that glutamine deprivation resulted in decreased cell proliferation, time-dependent- and cell line-dependent ROS generation, aberrant mitochondrial membrane potential and disrupted cell cycle progression. In addition, the estrogen receptor positive MCF-7 cell line was more prominently affected. This study contributes to knowledge regarding the sensitivity of breast cancer cells and non-tumorigenic cells to glutamine deprivation.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.52 20192019-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100213en10.1186/s40659-019-0224-9
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Glutamine deprivation ROS Mitochondrial membrane potential Cell cycle progression Apoptosis
spellingShingle	Glutamine deprivation ROS Mitochondrial membrane potential Cell cycle progression Apoptosis Gwangwa,Mokgadi Violet Joubert,Anna Margaretha Visagie,Michelle Helen Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines
description	Abstract Background: Tumourigenic cells modify metabolic pathways In order to facilitate increased proliferation and cell survival resulting in glucose-and glutamine addiction. Previous research indicated that glutamine deprivation resulted in potential differential activity targeting tumourigenic cells more prominently. This is ascribed to tumourigenic cells utilising increased glutamine quantities for enhanced glycolysis-and glutaminolysis. In this study, the effects exerted by glutamine deprivation on reactive oxygen species (ROS) production, mitochondrial membrane potential, cell proliferation and cell death in breast tumourigenic cell lines (MCF-7, MDA-MB-231, BT-20) and a non-tumourigenic breast cell line (MCF-10A) were investigated. Results: Spectrophotometry demonstrated that glutamine deprivation resulted in decreased cell growth in a time-dependent manner. MCF-7 cell growth was decreased to 61% after 96 h of glutamine deprivation; MDA-MB-231 cell growth was decreased to 78% cell growth after 96 h of glutamine deprivation, MCF-10A cell growth was decreased 89% after 96 h of glutamine deprivation and BT-20 cell growth decreased to 86% after 24 h of glutamine deprivation and remained unchanged until 96 h of glutamine deprivation. Glutamine deprivation resulted in oxidative stress where superoxide levels were significantly elevated after 96 h in the MCF-7-and MDA-MB-231 cell lines. Time-dependent production of hydrogen peroxide was accompanied by aberrant mitochondrial membrane potential. The effects of ROS and mitochondrial membrane potential were more prominently observed in the MCF-7 cell line when compared to the MDA-MB-231-, MCF-10A- and BT-20 cell lines. Cell cycle progression revealed that glutamine deprivation resulted in a significant increase in the S-phase after 72 h of glutamine deprivation in the MCF-7 cell line. Apoptosis induction resulted in a decrease in viable cells in all cell lines following glutamine deprivation. In the MCF-7 cells, 87.61% of viable cells were present after 24 h of glutamine deprivation. Conclusion: This study demonstrates that glutamine deprivation resulted in decreased cell proliferation, time-dependent- and cell line-dependent ROS generation, aberrant mitochondrial membrane potential and disrupted cell cycle progression. In addition, the estrogen receptor positive MCF-7 cell line was more prominently affected. This study contributes to knowledge regarding the sensitivity of breast cancer cells and non-tumorigenic cells to glutamine deprivation.
author	Gwangwa,Mokgadi Violet Joubert,Anna Margaretha Visagie,Michelle Helen
author_facet	Gwangwa,Mokgadi Violet Joubert,Anna Margaretha Visagie,Michelle Helen
author_sort	Gwangwa,Mokgadi Violet
title	Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines
title_short	Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines
title_full	Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines
title_fullStr	Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines
title_full_unstemmed	Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines
title_sort	effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines
publisher	Sociedad de Biología de Chile
publishDate	2019
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602019000100213
work_keys_str_mv	AT gwangwamokgadiviolet effectsofglutaminedeprivationonoxidativestressandcellsurvivalinbreastcelllines AT joubertannamargaretha effectsofglutaminedeprivationonoxidativestressandcellsurvivalinbreastcelllines AT visagiemichellehelen effectsofglutaminedeprivationonoxidativestressandcellsurvivalinbreastcelllines
_version_	1718441586995494912

Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines

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