Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line
Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin en...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2015-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/607957 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832558633252028416 |
|---|---|
| author | Isabella Massimi Ambra Ciuffetta Flavia Temperilli Francesca Ferrandino Alessandra Zicari Fabio M. Pulcinelli Maria Pia Felli |
| author_facet | Isabella Massimi Ambra Ciuffetta Flavia Temperilli Francesca Ferrandino Alessandra Zicari Fabio M. Pulcinelli Maria Pia Felli |
| author_sort | Isabella Massimi |
| collection | DOAJ |
| description | Overexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα). In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293) to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin. |
| format | Article |
| id | doaj-art-05c0f52772d541c6b41e1bccfdc1c777 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-05c0f52772d541c6b41e1bccfdc1c7772025-02-03T01:31:48ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/607957607957Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell LineIsabella Massimi0Ambra Ciuffetta1Flavia Temperilli2Francesca Ferrandino3Alessandra Zicari4Fabio M. Pulcinelli5Maria Pia Felli6Department of Experimental Medicine, Faculty of Medicine and Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Faculty of Medicine and Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Faculty of Medicine and Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Molecular Medicine, Faculty of Medicine and Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Faculty of Medicine and Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Faculty of Medicine and Surgery, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Experimental Medicine, Faculty of Medicine and Surgery, Sapienza University of Rome, 00161 Rome, ItalyOverexpression of efflux transporters, in human cells, is a mechanism of resistance to drug and also to chemotherapy. We found that multidrug resistance protein-4 (MRP4) overexpression has a role in reducing aspirin action in patients after bypass surgery and, very recently, we found that aspirin enhances platelet MRP4 levels through peroxisome proliferator activated receptor-α (PPARα). In the present paper, we verified whether exposure of human embryonic kidney-293 cells (Hek-293) to aspirin modifies MRP4 gene expression and its correlation with drug elimination and cell toxicity. We first investigated the effect of high-dose aspirin in Hek-293 and we showed that aspirin is able to increase cell toxicity dose-dependently. Furthermore, aspirin effects, induced at low dose, already enhance MRP4 gene expression. Based on these findings, we compared cell viability in Hek-293, after high-dose aspirin treatment, in MRP4 overexpressing cells, either after aspirin pretreatment or in MRP4 transfected cells; in both cases, a decrease of selective aspirin cell growth inhibition was observed, in comparison with the control cultures. Altogether, these data suggest that exposing cells to low nontoxic aspirin dosages can induce gene expression alterations that may lead to the efflux transporter protein overexpression, thus increasing cellular detoxification of aspirin.http://dx.doi.org/10.1155/2015/607957 |
| spellingShingle | Isabella Massimi Ambra Ciuffetta Flavia Temperilli Francesca Ferrandino Alessandra Zicari Fabio M. Pulcinelli Maria Pia Felli Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line Mediators of Inflammation |
| title | Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line |
| title_full | Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line |
| title_fullStr | Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line |
| title_full_unstemmed | Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line |
| title_short | Multidrug Resistance Protein-4 Influences Aspirin Toxicity in Human Cell Line |
| title_sort | multidrug resistance protein 4 influences aspirin toxicity in human cell line |
| url | http://dx.doi.org/10.1155/2015/607957 |
| work_keys_str_mv | AT isabellamassimi multidrugresistanceprotein4influencesaspirintoxicityinhumancellline AT ambraciuffetta multidrugresistanceprotein4influencesaspirintoxicityinhumancellline AT flaviatemperilli multidrugresistanceprotein4influencesaspirintoxicityinhumancellline AT francescaferrandino multidrugresistanceprotein4influencesaspirintoxicityinhumancellline AT alessandrazicari multidrugresistanceprotein4influencesaspirintoxicityinhumancellline AT fabiompulcinelli multidrugresistanceprotein4influencesaspirintoxicityinhumancellline AT mariapiafelli multidrugresistanceprotein4influencesaspirintoxicityinhumancellline |