pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells
Brazilian green propolis is a well-known product that is consumed globally. Its major component, Artepillin C, showed potential as an antitumor product. This study explored the impact of Artepillin C on fibroblast and glioblastoma cell lines, used as healthy and very aggressive tumor cell lines, res...
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| Format: | Article |
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MDPI AG
2023-11-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/13/11/2186 |
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| author | Wallance M. Pazin Renata R. Miranda Karina A. Toledo Frank Kjeldsen Carlos J. L. Constantino Jonathan R. Brewer |
| author_facet | Wallance M. Pazin Renata R. Miranda Karina A. Toledo Frank Kjeldsen Carlos J. L. Constantino Jonathan R. Brewer |
| author_sort | Wallance M. Pazin |
| collection | DOAJ |
| description | Brazilian green propolis is a well-known product that is consumed globally. Its major component, Artepillin C, showed potential as an antitumor product. This study explored the impact of Artepillin C on fibroblast and glioblastoma cell lines, used as healthy and very aggressive tumor cell lines, respectively. The focus of the study was to evaluate the pH-dependence of Artepillin C cytotoxicity, since tumor cells are known to have a more acidic extracellular microenvironment compared to healthy cells, and Artepillin C was shown to become more lipophilic at lower pH values. Investigations into the pH-dependency of Artepillin C (6.0–7.4), through viability assays and live cell imaging, revealed compelling insights. At pH 6.0, MTT assays showed the pronounced cytotoxic effects of Artepillin C, yielding a notable reduction in cell viability to less than 12% among glioblastoma cells following a 24 h exposure to 100 µM of Artepillin C. Concurrently, LDH assays indicated significant membrane damage, affecting approximately 50% of the total cells under the same conditions. Our Laurdan GP analysis suggests that Artepillin C induces autophagy, and notably, provokes a lipid membrane packing effect, contributing to cell death. These combined results affirm the selective cytotoxicity of Artepillin C within the acidic tumor microenvironment, emphasizing its potential as an effective antitumor agent. Furthermore, our findings suggest that Artepillin C holds promise for potential applications in the realm of anticancer therapies given its pH-dependence cytotoxicity. |
| first_indexed | 2024-03-09T16:40:20Z |
| format | Article |
| id | doaj.art-ae0ebaea3f894fc5bc952fcdcfca20c1 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T16:40:20Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-ae0ebaea3f894fc5bc952fcdcfca20c12023-11-24T14:52:30ZengMDPI AGLife2075-17292023-11-011311218610.3390/life13112186pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor CellsWallance M. Pazin0Renata R. Miranda1Karina A. Toledo2Frank Kjeldsen3Carlos J. L. Constantino4Jonathan R. Brewer5Department of Physics and Meteorology, School of Sciences, São Paulo State University (UNESP), Bauru 17033-360, BrazilDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Biological Sciences, School of Sciences, Humanities and Languages, São Paulo State University (UNESP), Assis 19806-900, BrazilDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Physics, School of Sciences and Technology, São Paulo State University (UNESP), Presidente Prudente 19060-900, BrazilDepartment of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkBrazilian green propolis is a well-known product that is consumed globally. Its major component, Artepillin C, showed potential as an antitumor product. This study explored the impact of Artepillin C on fibroblast and glioblastoma cell lines, used as healthy and very aggressive tumor cell lines, respectively. The focus of the study was to evaluate the pH-dependence of Artepillin C cytotoxicity, since tumor cells are known to have a more acidic extracellular microenvironment compared to healthy cells, and Artepillin C was shown to become more lipophilic at lower pH values. Investigations into the pH-dependency of Artepillin C (6.0–7.4), through viability assays and live cell imaging, revealed compelling insights. At pH 6.0, MTT assays showed the pronounced cytotoxic effects of Artepillin C, yielding a notable reduction in cell viability to less than 12% among glioblastoma cells following a 24 h exposure to 100 µM of Artepillin C. Concurrently, LDH assays indicated significant membrane damage, affecting approximately 50% of the total cells under the same conditions. Our Laurdan GP analysis suggests that Artepillin C induces autophagy, and notably, provokes a lipid membrane packing effect, contributing to cell death. These combined results affirm the selective cytotoxicity of Artepillin C within the acidic tumor microenvironment, emphasizing its potential as an effective antitumor agent. Furthermore, our findings suggest that Artepillin C holds promise for potential applications in the realm of anticancer therapies given its pH-dependence cytotoxicity.https://www.mdpi.com/2075-1729/13/11/2186Artepillin CBrazilian green propolisantitumor activitylive cell imaging |
| spellingShingle | Wallance M. Pazin Renata R. Miranda Karina A. Toledo Frank Kjeldsen Carlos J. L. Constantino Jonathan R. Brewer pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells Life Artepillin C Brazilian green propolis antitumor activity live cell imaging |
| title | pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells |
| title_full | pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells |
| title_fullStr | pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells |
| title_full_unstemmed | pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells |
| title_short | pH-Dependence Cytotoxicity Evaluation of Artepillin C against Tumor Cells |
| title_sort | ph dependence cytotoxicity evaluation of artepillin c against tumor cells |
| topic | Artepillin C Brazilian green propolis antitumor activity live cell imaging |
| url | https://www.mdpi.com/2075-1729/13/11/2186 |
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