Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells
Recently, selenium containing derivatives have attracted more attention in medicinal chemistry. In the present work, the anticancer activity of symmetrical selenoesters was investigated by studying the reversal of efflux pump-related and apoptosis resistance in sensitive and resistant human colon ad...
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/2/610 |
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| author | Bálint Rácz Annamária Kincses Krisztián Laczi Gábor Rákhely Enrique Domínguez-Álvarez Gabriella Spengler |
| author_facet | Bálint Rácz Annamária Kincses Krisztián Laczi Gábor Rákhely Enrique Domínguez-Álvarez Gabriella Spengler |
| author_sort | Bálint Rácz |
| collection | DOAJ |
| description | Recently, selenium containing derivatives have attracted more attention in medicinal chemistry. In the present work, the anticancer activity of symmetrical selenoesters was investigated by studying the reversal of efflux pump-related and apoptosis resistance in sensitive and resistant human colon adenocarcinoma cells expressing the ABCB1 protein. The combined effect of the compounds with doxorubicin was demonstrated with a checkerboard assay. The ABCB1 inhibitory and the apoptosis-inducing effects of the derivatives were measured with flow cytometry. Whole transcriptome sequencing was carried out on Illumina platform upon the treatment of resistant cells with the most potent derivatives. One ketone and three methyl ester selenoesters showed synergistic or weak synergistic interaction with doxorubicin, respectively. Ketone selenoesters were the most potent ABCB1 inhibitors and apoptosis inducers. Nitrile selenoesters could induce moderate early and late apoptotic processes that could be explained by their ABCB1 modulating properties. The transcriptome analysis revealed that symmetrical selenoesters may influence the redox state of the cells and interfere with metastasis formation. It can be assumed that these symmetrical selenocompounds possess toxic, DNA-damaging effects due to the presence of two selenium atoms in the molecule, which may be augmented by the presence of symmetrical groups. |
| first_indexed | 2024-03-11T08:17:05Z |
| format | Article |
| id | doaj.art-8dd9c3c575e743fabb0372b566cb9efe |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:17:05Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8dd9c3c575e743fabb0372b566cb9efe2023-11-16T22:42:17ZengMDPI AGPharmaceutics1999-49232023-02-0115261010.3390/pharmaceutics15020610Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma CellsBálint Rácz0Annamária Kincses1Krisztián Laczi2Gábor Rákhely3Enrique Domínguez-Álvarez4Gabriella Spengler5Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, HungaryDepartment of Biotechnology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, 6726 Szeged, HungaryDepartment of Biotechnology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, 6726 Szeged, HungaryInstituto de Química Orgánica General (IQOG), CSIC, Juan de la Cierva 3, 28006 Madrid, SpainDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center and Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis utca 6, 6725 Szeged, HungaryRecently, selenium containing derivatives have attracted more attention in medicinal chemistry. In the present work, the anticancer activity of symmetrical selenoesters was investigated by studying the reversal of efflux pump-related and apoptosis resistance in sensitive and resistant human colon adenocarcinoma cells expressing the ABCB1 protein. The combined effect of the compounds with doxorubicin was demonstrated with a checkerboard assay. The ABCB1 inhibitory and the apoptosis-inducing effects of the derivatives were measured with flow cytometry. Whole transcriptome sequencing was carried out on Illumina platform upon the treatment of resistant cells with the most potent derivatives. One ketone and three methyl ester selenoesters showed synergistic or weak synergistic interaction with doxorubicin, respectively. Ketone selenoesters were the most potent ABCB1 inhibitors and apoptosis inducers. Nitrile selenoesters could induce moderate early and late apoptotic processes that could be explained by their ABCB1 modulating properties. The transcriptome analysis revealed that symmetrical selenoesters may influence the redox state of the cells and interfere with metastasis formation. It can be assumed that these symmetrical selenocompounds possess toxic, DNA-damaging effects due to the presence of two selenium atoms in the molecule, which may be augmented by the presence of symmetrical groups.https://www.mdpi.com/1999-4923/15/2/610multidrug resistanceP-glycoprotein or ABCB1apoptosisselenoestersmetastasis |
| spellingShingle | Bálint Rácz Annamária Kincses Krisztián Laczi Gábor Rákhely Enrique Domínguez-Álvarez Gabriella Spengler Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells Pharmaceutics multidrug resistance P-glycoprotein or ABCB1 apoptosis selenoesters metastasis |
| title | Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells |
| title_full | Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells |
| title_fullStr | Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells |
| title_full_unstemmed | Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells |
| title_short | Reversal of Multidrug Resistance by Symmetrical Selenoesters in Colon Adenocarcinoma Cells |
| title_sort | reversal of multidrug resistance by symmetrical selenoesters in colon adenocarcinoma cells |
| topic | multidrug resistance P-glycoprotein or ABCB1 apoptosis selenoesters metastasis |
| url | https://www.mdpi.com/1999-4923/15/2/610 |
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