Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells
Abstract Background Development of multidrug resistance (MDR) is a major burden of successful chemotherapy, therefore, novel approaches to defeat MDR are imperative. Although the remarkable anti-cancer propensity of silver nanoparticles (AgNP) has been demonstrated and their potential application in...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-019-0448-4 |
| _version_ | 1798024276902674432 |
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| author | Mohana Krishna Gopisetty Dávid Kovács Nóra Igaz Andrea Rónavári Péter Bélteky Zsolt Rázga Viktória Venglovecz Bálint Csoboz Imre Miklós Boros Zoltán Kónya Mónika Kiricsi |
| author_facet | Mohana Krishna Gopisetty Dávid Kovács Nóra Igaz Andrea Rónavári Péter Bélteky Zsolt Rázga Viktória Venglovecz Bálint Csoboz Imre Miklós Boros Zoltán Kónya Mónika Kiricsi |
| author_sort | Mohana Krishna Gopisetty |
| collection | DOAJ |
| description | Abstract Background Development of multidrug resistance (MDR) is a major burden of successful chemotherapy, therefore, novel approaches to defeat MDR are imperative. Although the remarkable anti-cancer propensity of silver nanoparticles (AgNP) has been demonstrated and their potential application in MDR cancer has been proposed, the nanoparticle size-dependent cellular events directing P-glycoprotein (Pgp) expression and activity in MDR cancer have never been addressed. Hence, in the present study we examined AgNP size-dependent cellular features in multidrug resistant breast cancer cells. Results In this study we report that 75 nm AgNPs inhibited significantly Pgp efflux activity in drug-resistant breast cancer cells and potentiated the apoptotic effect of doxorubicin, which features were not observed upon 5 nm AgNP treatment. Although both sized AgNPs induced significant ROS production and mitochondrial damage, 5 nm AgNPs were more potent than 75 nm AgNPs in this respect, therefore, these effects can not to be accounted for the reduced transport activity of ATP-driven pumps observed after 75 nm AgNP treatments. Instead we found that 75 nm AgNPs depleted endoplasmic reticulum (ER) calcium stores, caused notable ER stress and decreased plasma membrane positioning of Pgp. Conclusion Our study suggests that AgNPs are potent inhibitors of Pgp function and are promising agents for sensitizing multidrug resistant breast cancers to anticancer drugs. This potency is determined by their size, since 75 nm AgNPs are more efficient than smaller counterparts. This is a highly relevant finding as it renders AgNPs attractive candidates in rational design of therapeutically useful agents for tumor targeting. In the present study we provide evidence that exploitation of ER stress can be a propitious target in defeating multidrug resistance in cancers. |
| first_indexed | 2024-04-11T17:59:49Z |
| format | Article |
| id | doaj.art-858371aa5760406795391201bfb630e0 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T17:59:49Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-858371aa5760406795391201bfb630e02022-12-22T04:10:32ZengBMCJournal of Nanobiotechnology1477-31552019-01-0117111510.1186/s12951-019-0448-4Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cellsMohana Krishna Gopisetty0Dávid Kovács1Nóra Igaz2Andrea Rónavári3Péter Bélteky4Zsolt Rázga5Viktória Venglovecz6Bálint Csoboz7Imre Miklós Boros8Zoltán Kónya9Mónika Kiricsi10Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of SzegedDepartment of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of SzegedDepartment of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of SzegedDepartment of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of SzegedDepartment of Applied and Environmental Chemistry, University of SzegedDepartment of Pathology, University of SzegedDepartment of Pharmacology and Pharmacotherapy, University of SzegedInstitute of Biochemistry, Biological Research Center of the Hungarian Academy of SciencesDepartment of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of SzegedDepartment of Applied and Environmental Chemistry, University of SzegedDepartment of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of SzegedAbstract Background Development of multidrug resistance (MDR) is a major burden of successful chemotherapy, therefore, novel approaches to defeat MDR are imperative. Although the remarkable anti-cancer propensity of silver nanoparticles (AgNP) has been demonstrated and their potential application in MDR cancer has been proposed, the nanoparticle size-dependent cellular events directing P-glycoprotein (Pgp) expression and activity in MDR cancer have never been addressed. Hence, in the present study we examined AgNP size-dependent cellular features in multidrug resistant breast cancer cells. Results In this study we report that 75 nm AgNPs inhibited significantly Pgp efflux activity in drug-resistant breast cancer cells and potentiated the apoptotic effect of doxorubicin, which features were not observed upon 5 nm AgNP treatment. Although both sized AgNPs induced significant ROS production and mitochondrial damage, 5 nm AgNPs were more potent than 75 nm AgNPs in this respect, therefore, these effects can not to be accounted for the reduced transport activity of ATP-driven pumps observed after 75 nm AgNP treatments. Instead we found that 75 nm AgNPs depleted endoplasmic reticulum (ER) calcium stores, caused notable ER stress and decreased plasma membrane positioning of Pgp. Conclusion Our study suggests that AgNPs are potent inhibitors of Pgp function and are promising agents for sensitizing multidrug resistant breast cancers to anticancer drugs. This potency is determined by their size, since 75 nm AgNPs are more efficient than smaller counterparts. This is a highly relevant finding as it renders AgNPs attractive candidates in rational design of therapeutically useful agents for tumor targeting. In the present study we provide evidence that exploitation of ER stress can be a propitious target in defeating multidrug resistance in cancers.http://link.springer.com/article/10.1186/s12951-019-0448-4Silver nanoparticlesMultidrug resistanceP-glycoproteinER stress |
| spellingShingle | Mohana Krishna Gopisetty Dávid Kovács Nóra Igaz Andrea Rónavári Péter Bélteky Zsolt Rázga Viktória Venglovecz Bálint Csoboz Imre Miklós Boros Zoltán Kónya Mónika Kiricsi Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells Journal of Nanobiotechnology Silver nanoparticles Multidrug resistance P-glycoprotein ER stress |
| title | Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells |
| title_full | Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells |
| title_fullStr | Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells |
| title_full_unstemmed | Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells |
| title_short | Endoplasmic reticulum stress: major player in size-dependent inhibition of P-glycoprotein by silver nanoparticles in multidrug-resistant breast cancer cells |
| title_sort | endoplasmic reticulum stress major player in size dependent inhibition of p glycoprotein by silver nanoparticles in multidrug resistant breast cancer cells |
| topic | Silver nanoparticles Multidrug resistance P-glycoprotein ER stress |
| url | http://link.springer.com/article/10.1186/s12951-019-0448-4 |
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