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Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies
Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modula...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589691/ https://www.ncbi.nlm.nih.gov/pubmed/33096917 http://dx.doi.org/10.3390/ph13100327 |
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author | Afonso de Lima, Carolina de Souza Bueno, Ian Lucas Nunes Siqueira Vasconcelos, Stanley Sciani, Juliana Mozer Ruiz, Ana Lúcia Tasca Gois Foglio, Mary Ann de Carvalho, João Ernesto Barbarini Longato, Giovanna |
author_facet | Afonso de Lima, Carolina de Souza Bueno, Ian Lucas Nunes Siqueira Vasconcelos, Stanley Sciani, Juliana Mozer Ruiz, Ana Lúcia Tasca Gois Foglio, Mary Ann de Carvalho, João Ernesto Barbarini Longato, Giovanna |
author_sort | Afonso de Lima, Carolina |
collection | PubMed |
description | Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modulating MDR, is highlighted. Many pharmacological studies report the ability of calcium channel blockers to reverse tumor resistance to chemotherapy drugs. Isolated for the first time from parsley, the phenylpropanoid apiole is described as a potent calcium channel inhibitor. Taking this into account, herein, the ability of apiole to potentiate the action of well-established chemotherapeutics in the clinic, as well as the compound’s relationship with the reversal of the resistance phenomenon by blocking P-gp, is reported. The association of apiole with both chemotherapeutic drugs doxorubicin and vincristine resulted in synergistic effect, in a concentration-dependent manner, as evaluated by the concentration reduction index. Molecular docking analysis demonstrated the affinity between apiole and the active site of P-gp, corroborating the inhibitory effect. Moreover, apiole demonstrated druglikeness, according to ADME analysis. In conclusion, apiole possibly blocks the active P-gp site, with strong binding energy, which, in turn, inhibits doxorubicin and vincristine efflux, increasing the antiproliferative response of these chemotherapeutic agents. |
format | Online Article Text |
id | pubmed-7589691 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75896912020-10-29 Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies Afonso de Lima, Carolina de Souza Bueno, Ian Lucas Nunes Siqueira Vasconcelos, Stanley Sciani, Juliana Mozer Ruiz, Ana Lúcia Tasca Gois Foglio, Mary Ann de Carvalho, João Ernesto Barbarini Longato, Giovanna Pharmaceuticals (Basel) Article Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modulating MDR, is highlighted. Many pharmacological studies report the ability of calcium channel blockers to reverse tumor resistance to chemotherapy drugs. Isolated for the first time from parsley, the phenylpropanoid apiole is described as a potent calcium channel inhibitor. Taking this into account, herein, the ability of apiole to potentiate the action of well-established chemotherapeutics in the clinic, as well as the compound’s relationship with the reversal of the resistance phenomenon by blocking P-gp, is reported. The association of apiole with both chemotherapeutic drugs doxorubicin and vincristine resulted in synergistic effect, in a concentration-dependent manner, as evaluated by the concentration reduction index. Molecular docking analysis demonstrated the affinity between apiole and the active site of P-gp, corroborating the inhibitory effect. Moreover, apiole demonstrated druglikeness, according to ADME analysis. In conclusion, apiole possibly blocks the active P-gp site, with strong binding energy, which, in turn, inhibits doxorubicin and vincristine efflux, increasing the antiproliferative response of these chemotherapeutic agents. MDPI 2020-10-21 /pmc/articles/PMC7589691/ /pubmed/33096917 http://dx.doi.org/10.3390/ph13100327 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Afonso de Lima, Carolina de Souza Bueno, Ian Lucas Nunes Siqueira Vasconcelos, Stanley Sciani, Juliana Mozer Ruiz, Ana Lúcia Tasca Gois Foglio, Mary Ann de Carvalho, João Ernesto Barbarini Longato, Giovanna Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies |
title | Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies |
title_full | Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies |
title_fullStr | Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies |
title_full_unstemmed | Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies |
title_short | Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies |
title_sort | reversal of ovarian cancer cell lines multidrug resistance phenotype by the association of apiole with chemotherapies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589691/ https://www.ncbi.nlm.nih.gov/pubmed/33096917 http://dx.doi.org/10.3390/ph13100327 |
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