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 c...
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| Format: | Article |
| Language: | English |
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BMC
2019-03-01
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| Series: | Biological Research |
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| Online Access: | http://link.springer.com/article/10.1186/s40659-019-0224-9 |
| _version_ | 1828468042616537088 |
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| author | Mokgadi Violet Gwangwa Anna Margaretha Joubert Michelle Helen Visagie |
| author_facet | Mokgadi Violet Gwangwa Anna Margaretha Joubert Michelle Helen Visagie |
| author_sort | Mokgadi Violet Gwangwa |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T04:17:14Z |
| format | Article |
| id | doaj.art-1d8d163dd9ca4bdab6e425234b8825d2 |
| institution | Directory Open Access Journal |
| issn | 0717-6287 |
| language | English |
| last_indexed | 2024-12-11T04:17:14Z |
| publishDate | 2019-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj.art-1d8d163dd9ca4bdab6e425234b8825d22022-12-22T01:21:13ZengBMCBiological Research0717-62872019-03-0152111610.1186/s40659-019-0224-9Effects of glutamine deprivation on oxidative stress and cell survival in breast cell linesMokgadi Violet Gwangwa0Anna Margaretha Joubert1Michelle Helen Visagie2Department of Physiology, Faculty of Health Sciences, University of PretoriaDepartment of Physiology, Faculty of Health Sciences, University of PretoriaDepartment of Physiology, Faculty of Health Sciences, University of PretoriaAbstract 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.http://link.springer.com/article/10.1186/s40659-019-0224-9Glutamine deprivationROSMitochondrial membrane potentialCell cycle progressionApoptosis |
| spellingShingle | Mokgadi Violet Gwangwa Anna Margaretha Joubert Michelle Helen Visagie Effects of glutamine deprivation on oxidative stress and cell survival in breast cell lines Biological Research Glutamine deprivation ROS Mitochondrial membrane potential Cell cycle progression Apoptosis |
| title | 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_short | 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 |
| topic | Glutamine deprivation ROS Mitochondrial membrane potential Cell cycle progression Apoptosis |
| url | http://link.springer.com/article/10.1186/s40659-019-0224-9 |
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