Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells
Multidrug resistance (MDR) is a process that constitutes a significant obstacle to effective anticancer therapy. Here, we examined whether unsymmetrical bisacridines (UAs) are substrates for ABC transporters and can influence their expression in human colon LS 174T and prostate DU 145 cancer cells....
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2024-11-01
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| author | Monika Pawłowska Jolanta Kulesza Ewa Paluszkiewicz Ewa Augustin Zofia Mazerska |
| author_facet | Monika Pawłowska Jolanta Kulesza Ewa Paluszkiewicz Ewa Augustin Zofia Mazerska |
| author_sort | Monika Pawłowska |
| collection | DOAJ |
| description | Multidrug resistance (MDR) is a process that constitutes a significant obstacle to effective anticancer therapy. Here, we examined whether unsymmetrical bisacridines (UAs) are substrates for ABC transporters and can influence their expression in human colon LS 174T and prostate DU 145 cancer cells. Moreover, we investigated the cytotoxicity and the cellular response induced by UAs in these cells. The ATPase activities of MDR1, MRP1, and MRP2 were measured using vesicles prepared from insect Sf9 cells expressing particular ABC transporters. The gene expression and protein levels were analyzed using qPCR and Western blotting. The cellular effects were studied by MTT (cytotoxicity), flow cytometry (cell cycle analysis and phosphatidylserine externalization), and fluorescence microscopy. We showed that UAs are substrates for MDR1. Importantly, they did not influence remarkably the expressions of the <i>ABCB1</i>, <i>ABCC1</i>, and <i>ABCC2</i> genes and the levels of the MDR1 and PXR proteins in the studied cells. Furthermore, the cytotoxicity and the level of apoptosis triggered by UAs in LS 174T cells possessing higher expressions of metabolic enzymes were lower compared with DU 145 cells. These results indicate that during possible UA treatment, the occurrence of drug resistance could be limited, which could favor the use of such compounds as potential candidates for future studies. |
| format | Article |
| id | doaj-art-302cf8746ea24b5f99dfabb8470f7573 |
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| issn | 1420-3049 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| spelling | doaj-art-302cf8746ea24b5f99dfabb8470f75732025-08-20T01:55:38ZengMDPI AGMolecules1420-30492024-11-012923558210.3390/molecules29235582Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer CellsMonika Pawłowska0Jolanta Kulesza1Ewa Paluszkiewicz2Ewa Augustin3Zofia Mazerska4Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdańsk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdańsk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdańsk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdańsk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdańsk University of Technology, Gabriela Narutowicza Str. 11/12, 80-233 Gdańsk, PolandMultidrug resistance (MDR) is a process that constitutes a significant obstacle to effective anticancer therapy. Here, we examined whether unsymmetrical bisacridines (UAs) are substrates for ABC transporters and can influence their expression in human colon LS 174T and prostate DU 145 cancer cells. Moreover, we investigated the cytotoxicity and the cellular response induced by UAs in these cells. The ATPase activities of MDR1, MRP1, and MRP2 were measured using vesicles prepared from insect Sf9 cells expressing particular ABC transporters. The gene expression and protein levels were analyzed using qPCR and Western blotting. The cellular effects were studied by MTT (cytotoxicity), flow cytometry (cell cycle analysis and phosphatidylserine externalization), and fluorescence microscopy. We showed that UAs are substrates for MDR1. Importantly, they did not influence remarkably the expressions of the <i>ABCB1</i>, <i>ABCC1</i>, and <i>ABCC2</i> genes and the levels of the MDR1 and PXR proteins in the studied cells. Furthermore, the cytotoxicity and the level of apoptosis triggered by UAs in LS 174T cells possessing higher expressions of metabolic enzymes were lower compared with DU 145 cells. These results indicate that during possible UA treatment, the occurrence of drug resistance could be limited, which could favor the use of such compounds as potential candidates for future studies.https://www.mdpi.com/1420-3049/29/23/5582anticancer agentsunsymmetrical bisacridinesABC transportersmultidrug resistance (MDR)cytotoxicitycellular response |
| spellingShingle | Monika Pawłowska Jolanta Kulesza Ewa Paluszkiewicz Ewa Augustin Zofia Mazerska Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells Molecules anticancer agents unsymmetrical bisacridines ABC transporters multidrug resistance (MDR) cytotoxicity cellular response |
| title | Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells |
| title_full | Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells |
| title_fullStr | Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells |
| title_full_unstemmed | Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells |
| title_short | Unsymmetrical Bisacridines’ Interactions with ABC Transporters and Their Cellular Impact on Colon LS 174T and Prostate DU 145 Cancer Cells |
| title_sort | unsymmetrical bisacridines interactions with abc transporters and their cellular impact on colon ls 174t and prostate du 145 cancer cells |
| topic | anticancer agents unsymmetrical bisacridines ABC transporters multidrug resistance (MDR) cytotoxicity cellular response |
| url | https://www.mdpi.com/1420-3049/29/23/5582 |
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