<em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism
Breast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Ri...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/4219 |
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| author | Reem H. AlMalki Rajaa Sebaa Mysoon M. Al-Ansari Monther Al-Alwan Moudi A. Alwehaibi Anas M. Abdel Rahman |
| author_facet | Reem H. AlMalki Rajaa Sebaa Mysoon M. Al-Ansari Monther Al-Alwan Moudi A. Alwehaibi Anas M. Abdel Rahman |
| author_sort | Reem H. AlMalki |
| collection | DOAJ |
| description | Breast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Risk factors can also enhance it, including age, lifestyle, hormone disturbances, etc. Other unknown BC-promoting risk factors are under scientific investigation. One of these investigated factors is the microbiome. However, whether the breast microbiome found in the BC tissue microenvironment can impact BC cells has not been studied. We hypothesized that <i>E. coli</i>, part of a normal breast microbiome with more presence in BC tissue, secretes metabolic molecules that could alter BC cells’ metabolism to maintain their survival. Thus, we directly examined the impact of the <i>E. coli</i> secretome on the metabolism of BC cells in vitro. MDA-MB-231 cells, an in vitro model of aggressive triple-negative BC cells, were treated with the <i>E. coli</i> secretome at different time points, followed by untargeted metabolomics analyses via liquid chromatography–mass spectrometry to identify metabolic alterations in the treated BC cell lines. MDA-MB-231 cells that were not treated were used as controls. Moreover, metabolomic analyses were performed on the <i>E. coli</i> secretome to profile the most significant bacterial metabolites affecting the metabolism of the treated BC cell lines. The metabolomics results revealed about 15 metabolites that potentially have indirect roles in cancer metabolism that were secreted from <i>E. coli</i> in the culture media of MDA-MB-231 cells. The cells treated with the <i>E. coli</i> secretome showed 105 dysregulated cellular metabolites compared to controls. The dysregulated cellular metabolites were involved in the metabolism of fructose and mannose, sphingolipids, amino acids, fatty acids, amino sugar, nucleotide sugar, and pyrimidine, which are vital pathways required for the pathogenesis of BC. Our findings are the first to show that the <i>E. coli</i> secretome modulates the BC cells’ energy metabolism, highlighting insights into the possibility of altered metabolic events in BC tissue in the actual BC tissue microenvironment that are potentially induced by the local bacteria. Our study provides metabolic data that could be as a basis for future studies searching for the underlying mechanisms mediated by bacteria and their secretome to alter the metabolism of BC cells. |
| first_indexed | 2024-03-11T08:39:26Z |
| format | Article |
| id | doaj.art-2237aa406b2948569abbe9b4d39c9f49 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:39:26Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2237aa406b2948569abbe9b4d39c9f492023-11-16T21:11:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244421910.3390/ijms24044219<em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy MetabolismReem H. AlMalki0Rajaa Sebaa1Mysoon M. Al-Ansari2Monther Al-Alwan3Moudi A. Alwehaibi4Anas M. Abdel Rahman5Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Medical Laboratories, College of Applied Medical Sciences, Shaqra University, Al-Dawadmi 17472, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaStem Cell and Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi ArabiaDepartment of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi ArabiaMetabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi ArabiaBreast cancer (BC) is commonly diagnosed in women. BC cells are associated with altered metabolism, which is essential to support their energetic requirements, cellular proliferation, and continuous survival. The altered metabolism of BC cells is a result of the genetic abnormalities of BC cells. Risk factors can also enhance it, including age, lifestyle, hormone disturbances, etc. Other unknown BC-promoting risk factors are under scientific investigation. One of these investigated factors is the microbiome. However, whether the breast microbiome found in the BC tissue microenvironment can impact BC cells has not been studied. We hypothesized that <i>E. coli</i>, part of a normal breast microbiome with more presence in BC tissue, secretes metabolic molecules that could alter BC cells’ metabolism to maintain their survival. Thus, we directly examined the impact of the <i>E. coli</i> secretome on the metabolism of BC cells in vitro. MDA-MB-231 cells, an in vitro model of aggressive triple-negative BC cells, were treated with the <i>E. coli</i> secretome at different time points, followed by untargeted metabolomics analyses via liquid chromatography–mass spectrometry to identify metabolic alterations in the treated BC cell lines. MDA-MB-231 cells that were not treated were used as controls. Moreover, metabolomic analyses were performed on the <i>E. coli</i> secretome to profile the most significant bacterial metabolites affecting the metabolism of the treated BC cell lines. The metabolomics results revealed about 15 metabolites that potentially have indirect roles in cancer metabolism that were secreted from <i>E. coli</i> in the culture media of MDA-MB-231 cells. The cells treated with the <i>E. coli</i> secretome showed 105 dysregulated cellular metabolites compared to controls. The dysregulated cellular metabolites were involved in the metabolism of fructose and mannose, sphingolipids, amino acids, fatty acids, amino sugar, nucleotide sugar, and pyrimidine, which are vital pathways required for the pathogenesis of BC. Our findings are the first to show that the <i>E. coli</i> secretome modulates the BC cells’ energy metabolism, highlighting insights into the possibility of altered metabolic events in BC tissue in the actual BC tissue microenvironment that are potentially induced by the local bacteria. Our study provides metabolic data that could be as a basis for future studies searching for the underlying mechanisms mediated by bacteria and their secretome to alter the metabolism of BC cells.https://www.mdpi.com/1422-0067/24/4/4219microbiome<i>E. coli</i> secretomebreast cancer cellsmetabolitesmetabolomicshigh-resolution mass spectrometry |
| spellingShingle | Reem H. AlMalki Rajaa Sebaa Mysoon M. Al-Ansari Monther Al-Alwan Moudi A. Alwehaibi Anas M. Abdel Rahman <em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism International Journal of Molecular Sciences microbiome <i>E. coli</i> secretome breast cancer cells metabolites metabolomics high-resolution mass spectrometry |
| title | <em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
| title_full | <em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
| title_fullStr | <em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
| title_full_unstemmed | <em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
| title_short | <em>E. coli</em> Secretome Metabolically Modulates MDA-MB-231 Breast Cancer Cells’ Energy Metabolism |
| title_sort | em e coli em secretome metabolically modulates mda mb 231 breast cancer cells energy metabolism |
| topic | microbiome <i>E. coli</i> secretome breast cancer cells metabolites metabolomics high-resolution mass spectrometry |
| url | https://www.mdpi.com/1422-0067/24/4/4219 |
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