The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells
Multidrug resistance (MDR) is a major obstacle to the successful chemotherapy of solid tumors. We compared the resistance of the most popular solid tumors, breast adenocarcinoma (MCF-7 cell line) and nonsmall cell lung (A549 cell line) hepatocellular liver carcinoma (HepG2 cells), to aclarubicin (AC...
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Wiley
2014-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1155/2014/819548 |
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| author | Aneta Rogalska Marzena Szwed Błażej Rychlik |
| author_facet | Aneta Rogalska Marzena Szwed Błażej Rychlik |
| author_sort | Aneta Rogalska |
| collection | DOAJ |
| description | Multidrug resistance (MDR) is a major obstacle to the successful chemotherapy of solid tumors. We compared the resistance of the most popular solid tumors, breast adenocarcinoma (MCF-7 cell line) and nonsmall cell lung (A549 cell line) hepatocellular liver carcinoma (HepG2 cells), to aclarubicin (ACL) and doxorubicin (DOX). This research aimed at determining the relation between the toxicity of ACL and DOX, their cell accumulation, and then effect on P-glycoprotein functionality. ACL is more cytotoxic for tumor cells compared to DOX. The intracellular concentration of drugs in cancer cells was dependent on the dose of the drugs and the time of incubation. The P-gp inhibitor Verapamil (V) increased DOX accumulation in all tested cell lines. By contrast, the intracellular level of ACL was not affected by this modifying agent. The assessment of the uptake of 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide (JC-1) or Rhodamine 123 (R123) allows the evaluation of the different influence of drugs on P-gp activity which is in agreement with the estimation of expression measured by MDR-1 shift assay. These data suggest that ACL is less P-gp dependent than DOX and consequently may be used in a clinical setting to increase treatment efficacy in resistant human tumors. |
| format | Article |
| id | doaj-art-d21da719dc7b484398de7410fbbd0e08 |
| institution | OA Journals |
| issn | 2356-6140 1537-744X |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-d21da719dc7b484398de7410fbbd0e082025-08-20T02:19:42ZengWileyThe Scientific World Journal2356-61401537-744X2014-01-01201410.1155/2014/819548819548The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 CellsAneta Rogalska0Marzena Szwed1Błażej Rychlik2Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, PolandDepartment of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, PolandDepartment of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, PolandMultidrug resistance (MDR) is a major obstacle to the successful chemotherapy of solid tumors. We compared the resistance of the most popular solid tumors, breast adenocarcinoma (MCF-7 cell line) and nonsmall cell lung (A549 cell line) hepatocellular liver carcinoma (HepG2 cells), to aclarubicin (ACL) and doxorubicin (DOX). This research aimed at determining the relation between the toxicity of ACL and DOX, their cell accumulation, and then effect on P-glycoprotein functionality. ACL is more cytotoxic for tumor cells compared to DOX. The intracellular concentration of drugs in cancer cells was dependent on the dose of the drugs and the time of incubation. The P-gp inhibitor Verapamil (V) increased DOX accumulation in all tested cell lines. By contrast, the intracellular level of ACL was not affected by this modifying agent. The assessment of the uptake of 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide (JC-1) or Rhodamine 123 (R123) allows the evaluation of the different influence of drugs on P-gp activity which is in agreement with the estimation of expression measured by MDR-1 shift assay. These data suggest that ACL is less P-gp dependent than DOX and consequently may be used in a clinical setting to increase treatment efficacy in resistant human tumors.http://dx.doi.org/10.1155/2014/819548 |
| spellingShingle | Aneta Rogalska Marzena Szwed Błażej Rychlik The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells The Scientific World Journal |
| title | The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells |
| title_full | The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells |
| title_fullStr | The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells |
| title_full_unstemmed | The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells |
| title_short | The Connection between the Toxicity of Anthracyclines and Their Ability to Modulate the P-Glycoprotein-Mediated Transport in A549, HepG2, and MCF-7 Cells |
| title_sort | connection between the toxicity of anthracyclines and their ability to modulate the p glycoprotein mediated transport in a549 hepg2 and mcf 7 cells |
| url | http://dx.doi.org/10.1155/2014/819548 |
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