Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids
Plant-derived pentacyclic triterpenic acids (TAs) have gained increasing attention due to their multiple biological activities. Betulinic acid (BA) and ursolic acid (UA) modulate diverse pathways in carcinogenesis, offering increased changes of success in refractory cancers, such as triple negative...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/8/1163 |
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| author | Ângela R. Guerra Ana F. Paulino Maria M. Castro Helena Oliveira Maria F. Duarte Iola F. Duarte |
| author_facet | Ângela R. Guerra Ana F. Paulino Maria M. Castro Helena Oliveira Maria F. Duarte Iola F. Duarte |
| author_sort | Ângela R. Guerra |
| collection | DOAJ |
| description | Plant-derived pentacyclic triterpenic acids (TAs) have gained increasing attention due to their multiple biological activities. Betulinic acid (BA) and ursolic acid (UA) modulate diverse pathways in carcinogenesis, offering increased changes of success in refractory cancers, such as triple negative breast cancer (TNBC). The present work aimed to assess the metabolic effects of BA and UA in MDA-MB-231 breast cancer cells (TNBC model), as well as in MCF-10A non-cancer breast epithelial cells, with a view to unveiling the involvement of metabolic reprogramming in cellular responses to these TAs. Cell viability and cell cycle analyses were followed by assessment of changes in the cells exo- and endometabolome through <sup>1</sup>H NMR analysis of cell culture medium supernatants, aqueous and organic cell extracts. In MDA-MB-231 cells, BA was suggested to induce a transient upregulation of glucose consumption and glycolytic conversion, tricarboxylic acid (TCA) cycle intensification, and hydrolysis of neutral lipids, while UA effects were much less pronounced. In MCF-10A cells, boosting of glucose metabolism by the two TAs was accompanied by diversion of glycolytic intermediates to the hexosamine biosynthetic pathway (HBP) and the synthesis of neutral lipids, possibly stored in detoxifying lipid droplets. Additionally, breast epithelial cells intensified pyruvate consumption and TCA cycle activity, possibly to compensate for oxidative impairment of pyruvate glycolytic production. This study provided novel insights into the metabolic effects of BA and UA in cancer and non-cancer breast cells, thus improving current understanding of the action of these compounds at the molecular level. |
| first_indexed | 2024-03-10T17:46:03Z |
| format | Article |
| id | doaj.art-9e05edd3ce2d4bd0aaaa62bab0088858 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T17:46:03Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-9e05edd3ce2d4bd0aaaa62bab00888582023-11-20T09:32:31ZengMDPI AGBiomolecules2218-273X2020-08-01108116310.3390/biom10081163Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic AcidsÂngela R. Guerra0Ana F. Paulino1Maria M. Castro2Helena Oliveira3Maria F. Duarte4Iola F. Duarte5Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, PortugalCentro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), Apartado 6158, 7801-908 Beja, PortugalCentro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), Apartado 6158, 7801-908 Beja, PortugalDepartment of Biology & CESAM, University of Aveiro, 3810-193 Aveiro, PortugalCentro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja), Apartado 6158, 7801-908 Beja, PortugalDepartment of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, PortugalPlant-derived pentacyclic triterpenic acids (TAs) have gained increasing attention due to their multiple biological activities. Betulinic acid (BA) and ursolic acid (UA) modulate diverse pathways in carcinogenesis, offering increased changes of success in refractory cancers, such as triple negative breast cancer (TNBC). The present work aimed to assess the metabolic effects of BA and UA in MDA-MB-231 breast cancer cells (TNBC model), as well as in MCF-10A non-cancer breast epithelial cells, with a view to unveiling the involvement of metabolic reprogramming in cellular responses to these TAs. Cell viability and cell cycle analyses were followed by assessment of changes in the cells exo- and endometabolome through <sup>1</sup>H NMR analysis of cell culture medium supernatants, aqueous and organic cell extracts. In MDA-MB-231 cells, BA was suggested to induce a transient upregulation of glucose consumption and glycolytic conversion, tricarboxylic acid (TCA) cycle intensification, and hydrolysis of neutral lipids, while UA effects were much less pronounced. In MCF-10A cells, boosting of glucose metabolism by the two TAs was accompanied by diversion of glycolytic intermediates to the hexosamine biosynthetic pathway (HBP) and the synthesis of neutral lipids, possibly stored in detoxifying lipid droplets. Additionally, breast epithelial cells intensified pyruvate consumption and TCA cycle activity, possibly to compensate for oxidative impairment of pyruvate glycolytic production. This study provided novel insights into the metabolic effects of BA and UA in cancer and non-cancer breast cells, thus improving current understanding of the action of these compounds at the molecular level.https://www.mdpi.com/2218-273X/10/8/1163betulinic acidursolic acidtriple negative breast cancercell metabolismNMR metabolomics |
| spellingShingle | Ângela R. Guerra Ana F. Paulino Maria M. Castro Helena Oliveira Maria F. Duarte Iola F. Duarte Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids Biomolecules betulinic acid ursolic acid triple negative breast cancer cell metabolism NMR metabolomics |
| title | Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids |
| title_full | Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids |
| title_fullStr | Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids |
| title_full_unstemmed | Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids |
| title_short | Triple Negative Breast Cancer and Breast Epithelial Cells Differentially Reprogram Glucose and Lipid Metabolism upon Treatment with Triterpenic Acids |
| title_sort | triple negative breast cancer and breast epithelial cells differentially reprogram glucose and lipid metabolism upon treatment with triterpenic acids |
| topic | betulinic acid ursolic acid triple negative breast cancer cell metabolism NMR metabolomics |
| url | https://www.mdpi.com/2218-273X/10/8/1163 |
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