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Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin

Ecdysteroids, analogs of the insect molting hormone, are known for their various mild, nonhormonal bioactivities in mammals. Previously, we reported that less-polar ecdysteroids can modulate the doxorubicin resistance of a multidrug resistant (MDR) mouse lymphoma cell line expressing the human ABCB1...

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Autores principales: Martins, Ana, Sipos, Péter, Dér, Katalin, Csábi, József, Miklos, Walter, Berger, Walter, Zalatnai, Attila, Amaral, Leonard, Molnár, Joseph, Szabó-Révész, Piroska, Hunyadi, Attila
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449901/
https://www.ncbi.nlm.nih.gov/pubmed/26075272
http://dx.doi.org/10.1155/2015/895360
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author Martins, Ana
Sipos, Péter
Dér, Katalin
Csábi, József
Miklos, Walter
Berger, Walter
Zalatnai, Attila
Amaral, Leonard
Molnár, Joseph
Szabó-Révész, Piroska
Hunyadi, Attila
author_facet Martins, Ana
Sipos, Péter
Dér, Katalin
Csábi, József
Miklos, Walter
Berger, Walter
Zalatnai, Attila
Amaral, Leonard
Molnár, Joseph
Szabó-Révész, Piroska
Hunyadi, Attila
author_sort Martins, Ana
collection PubMed
description Ecdysteroids, analogs of the insect molting hormone, are known for their various mild, nonhormonal bioactivities in mammals. Previously, we reported that less-polar ecdysteroids can modulate the doxorubicin resistance of a multidrug resistant (MDR) mouse lymphoma cell line expressing the human ABCB1 transporter. Here, we describe the ability of 20-hydroxyecdysone (1) and its mono- (2) and diacetonide (3) derivatives to sensitize various MDR and non-MDR cancer cell lines towards doxorubicin, paclitaxel, vincristine, or cisplatin. Drug IC(50) values with or without ecdysteroid were determined by MTT assay. Compound 3 significantly sensitized all cell lines to each chemotherapeutic except for cisplatin, whose activity was decreased. In order to overcome solubility and stability issues for the future in vivo administration of compound 3, liposomal formulations were developed. By means of their combination index values obtained via checkerboard microplate method, a formulation showed superior activity to that of compound 3 alone. Because ecdysteroids act also on non-ABCB1 expressing (sensitive) cell lines, our results demonstrate that they do not or not exclusively exert their adjuvant anticancer activity as ABCB1 inhibitors, but other mechanisms must be involved, and they opened the way towards their in vivo bioactivity testing against various cancer xenografts.
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spelling pubmed-44499012015-06-14 Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin Martins, Ana Sipos, Péter Dér, Katalin Csábi, József Miklos, Walter Berger, Walter Zalatnai, Attila Amaral, Leonard Molnár, Joseph Szabó-Révész, Piroska Hunyadi, Attila Biomed Res Int Research Article Ecdysteroids, analogs of the insect molting hormone, are known for their various mild, nonhormonal bioactivities in mammals. Previously, we reported that less-polar ecdysteroids can modulate the doxorubicin resistance of a multidrug resistant (MDR) mouse lymphoma cell line expressing the human ABCB1 transporter. Here, we describe the ability of 20-hydroxyecdysone (1) and its mono- (2) and diacetonide (3) derivatives to sensitize various MDR and non-MDR cancer cell lines towards doxorubicin, paclitaxel, vincristine, or cisplatin. Drug IC(50) values with or without ecdysteroid were determined by MTT assay. Compound 3 significantly sensitized all cell lines to each chemotherapeutic except for cisplatin, whose activity was decreased. In order to overcome solubility and stability issues for the future in vivo administration of compound 3, liposomal formulations were developed. By means of their combination index values obtained via checkerboard microplate method, a formulation showed superior activity to that of compound 3 alone. Because ecdysteroids act also on non-ABCB1 expressing (sensitive) cell lines, our results demonstrate that they do not or not exclusively exert their adjuvant anticancer activity as ABCB1 inhibitors, but other mechanisms must be involved, and they opened the way towards their in vivo bioactivity testing against various cancer xenografts. Hindawi Publishing Corporation 2015 2015-05-17 /pmc/articles/PMC4449901/ /pubmed/26075272 http://dx.doi.org/10.1155/2015/895360 Text en Copyright © 2015 Ana Martins et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Martins, Ana
Sipos, Péter
Dér, Katalin
Csábi, József
Miklos, Walter
Berger, Walter
Zalatnai, Attila
Amaral, Leonard
Molnár, Joseph
Szabó-Révész, Piroska
Hunyadi, Attila
Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin
title Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin
title_full Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin
title_fullStr Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin
title_full_unstemmed Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin
title_short Ecdysteroids Sensitize MDR and Non-MDR Cancer Cell Lines to Doxorubicin, Paclitaxel, and Vincristine but Tend to Protect Them from Cisplatin
title_sort ecdysteroids sensitize mdr and non-mdr cancer cell lines to doxorubicin, paclitaxel, and vincristine but tend to protect them from cisplatin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449901/
https://www.ncbi.nlm.nih.gov/pubmed/26075272
http://dx.doi.org/10.1155/2015/895360
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