<i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer Cells

The conversion of betulinic acid (BA) to organic salts is a strategic approach to modulate its physicochemical properties and biological activity. In our previous study, we demonstrated the enhanced cytotoxicity of certain amino acid ethyl ester betulinates ([AAOEt][BA]) compared to BA against hormo...

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Main Authors: Sonia Apostolova, Irina Georgieva, Paula Ossowicz-Rupniewska, Joanna Klebeko, Svetla Todinova, Rumiana Tzoneva, Maya Guncheva
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Sci
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Online Access:https://www.mdpi.com/2413-4155/7/1/2
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author Sonia Apostolova
Irina Georgieva
Paula Ossowicz-Rupniewska
Joanna Klebeko
Svetla Todinova
Rumiana Tzoneva
Maya Guncheva
author_facet Sonia Apostolova
Irina Georgieva
Paula Ossowicz-Rupniewska
Joanna Klebeko
Svetla Todinova
Rumiana Tzoneva
Maya Guncheva
author_sort Sonia Apostolova
collection DOAJ
description The conversion of betulinic acid (BA) to organic salts is a strategic approach to modulate its physicochemical properties and biological activity. In our previous study, we demonstrated the enhanced cytotoxicity of certain amino acid ethyl ester betulinates ([AAOEt][BA]) compared to BA against hormone-dependent breast cancer cells (MCF-7). In this study, we extended our investigation to evaluate the cytotoxic response and thermodynamic properties of hormone-independent breast cancer cells (MDA-MB-231) following 72 h of treatment with the same series of betulinates. Our data reveal a lower cytotoxic response in MDA-MB-231 cells, indicated by higher half-maximal inhibitory concentration (IC<sub>50</sub>) values, which ranged between 31 and 109 μM. Differential scanning calorimetry analysis supported these findings, showing negligible changes in the thermodynamic parameters of the treated MDA-MB-231 cells. However, consistent with our previous observations, [LysOEt][BA]<sub>2</sub>, exhibited the highest cytotoxicity and induced the most pronounced morphological alterations in the cancer cells. Overall, our results suggest that MDA-MB-231 cells are less sensitive to [AAOEt][BA] compared to MCF-7 cells, likely due to their distinct phenotypic and genotypic profiles and differences in oncogenic signalling pathways. Nonetheless, the fact that [LysOEt][BA]<sub>2</sub> enhances the cytotoxic activity of BA even in hormone-independent breast cancer cells underscores its therapeutic potential and warrants further investigation, particularly in the context of adjuvant breast cancer therapy.
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spelling doaj-art-74a88dc2ef3245679318bafadc5df12f2025-08-20T01:49:07ZengMDPI AGSci2413-41552025-01-0171210.3390/sci7010002<i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer CellsSonia Apostolova0Irina Georgieva1Paula Ossowicz-Rupniewska2Joanna Klebeko3Svetla Todinova4Rumiana Tzoneva5Maya Guncheva6Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, 1113 Sofia, BulgariaDepartment of Chemical Organic Technology and Polymeric Materials, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology in Szczecin, Piastów Ave. 42, 71-065 Szczecin, PolandDepartment of Chemical Organic Technology and Polymeric Materials, Faculty of Chemical Technology and Engineering, West Pomeranian University of Technology in Szczecin, Piastów Ave. 42, 71-065 Szczecin, PolandInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, 1113 Sofia, BulgariaInstitute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 21, 1113 Sofia, BulgariaInstitute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 9, 1113 Sofia, BulgariaThe conversion of betulinic acid (BA) to organic salts is a strategic approach to modulate its physicochemical properties and biological activity. In our previous study, we demonstrated the enhanced cytotoxicity of certain amino acid ethyl ester betulinates ([AAOEt][BA]) compared to BA against hormone-dependent breast cancer cells (MCF-7). In this study, we extended our investigation to evaluate the cytotoxic response and thermodynamic properties of hormone-independent breast cancer cells (MDA-MB-231) following 72 h of treatment with the same series of betulinates. Our data reveal a lower cytotoxic response in MDA-MB-231 cells, indicated by higher half-maximal inhibitory concentration (IC<sub>50</sub>) values, which ranged between 31 and 109 μM. Differential scanning calorimetry analysis supported these findings, showing negligible changes in the thermodynamic parameters of the treated MDA-MB-231 cells. However, consistent with our previous observations, [LysOEt][BA]<sub>2</sub>, exhibited the highest cytotoxicity and induced the most pronounced morphological alterations in the cancer cells. Overall, our results suggest that MDA-MB-231 cells are less sensitive to [AAOEt][BA] compared to MCF-7 cells, likely due to their distinct phenotypic and genotypic profiles and differences in oncogenic signalling pathways. Nonetheless, the fact that [LysOEt][BA]<sub>2</sub> enhances the cytotoxic activity of BA even in hormone-independent breast cancer cells underscores its therapeutic potential and warrants further investigation, particularly in the context of adjuvant breast cancer therapy.https://www.mdpi.com/2413-4155/7/1/2betulinic acidionic liquidstriple-negative breast cancercytotoxicitydifferential scanning calorimetry
spellingShingle Sonia Apostolova
Irina Georgieva
Paula Ossowicz-Rupniewska
Joanna Klebeko
Svetla Todinova
Rumiana Tzoneva
Maya Guncheva
<i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer Cells
Sci
betulinic acid
ionic liquids
triple-negative breast cancer
cytotoxicity
differential scanning calorimetry
title <i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer Cells
title_full <i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer Cells
title_fullStr <i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer Cells
title_full_unstemmed <i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer Cells
title_short <i>In Vitro</i> Cytotoxicity Assessment of Betulinic Acid Organic Salts on Triple-Negative Breast Cancer Cells
title_sort i in vitro i cytotoxicity assessment of betulinic acid organic salts on triple negative breast cancer cells
topic betulinic acid
ionic liquids
triple-negative breast cancer
cytotoxicity
differential scanning calorimetry
url https://www.mdpi.com/2413-4155/7/1/2
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