<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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Summary: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.
ISSN:2413-4155