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Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin

BACKGROUND: In order to obtain better clinical results in anticancer therapies, polychemotherapy or combination therapies are used. For this, the combinations are required to increase the efficacy and reduce the adverse reactions of the associated chemotherapies. The aim of this study was to evaluat...

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Autores principales: de Oliveira Mauro, Mariana, Matuo, Renata, de David, Natan, Strapasson, Regiane Lauriano Batista, Oliveira, Rodrigo Juliano, Stefanello, Maria Élida Alves, Kassuya, Cândida Aparecida Leite, de Cepa Matos, Maria de Fátima, Faria, Fábio José Carvalho, Costa, Deiler Sampaio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492432/
https://www.ncbi.nlm.nih.gov/pubmed/28662728
http://dx.doi.org/10.1186/s40360-017-0156-3
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author de Oliveira Mauro, Mariana
Matuo, Renata
de David, Natan
Strapasson, Regiane Lauriano Batista
Oliveira, Rodrigo Juliano
Stefanello, Maria Élida Alves
Kassuya, Cândida Aparecida Leite
de Cepa Matos, Maria de Fátima
Faria, Fábio José Carvalho
Costa, Deiler Sampaio
author_facet de Oliveira Mauro, Mariana
Matuo, Renata
de David, Natan
Strapasson, Regiane Lauriano Batista
Oliveira, Rodrigo Juliano
Stefanello, Maria Élida Alves
Kassuya, Cândida Aparecida Leite
de Cepa Matos, Maria de Fátima
Faria, Fábio José Carvalho
Costa, Deiler Sampaio
author_sort de Oliveira Mauro, Mariana
collection PubMed
description BACKGROUND: In order to obtain better clinical results in anticancer therapies, polychemotherapy or combination therapies are used. For this, the combinations are required to increase the efficacy and reduce the adverse reactions of the associated chemotherapies. The aim of this study was to evaluate the cytotoxic, apoptotic and (anti)proliferative potential of two sesquiterpene lactones isolated from Moquiniastrum polymorphum, 11,13-diidrozaluzanin C (1) and gochnatiolide C (2), and their associations with chemotherapeutic agents irinotecan, tamoxifen, cisplatin, 5-fluouracyl and doxorubicin in the tumoral lineage of MCF-7 breast adenocarcinoma. METHODS: The analyses were performed by MTT cytotoxicity assays, drug combination index (CI), apoptosis morphological assay and cell proliferation assay. Treatments were evaluated with short exposure times (4 h), followed or not by recovery in drug-free medium for 24 h. For the cell viability assay the statistical analysis was performed using software INSTAT, and the ANOVA/Tukey test was applied. Combination Indices (CI) was made using CompuSyn software and demonstrated through isoboles. The assays that evaluated cell death and proliferation used statistical analysis SAS 9.4 (Statistical Analysis System), and the procedure adopted was PROC NPAR1WAY. The Wilcoxon test at 5% level was applied for comparing statistical differences. RESULTS: The results demonstrated that the compounds decrease cell viability and increase their action when associated with irinotecan, tamoxifen and doxorubicin (CI < 1 and CI = 1). In periods of 4 h-exposure, the compounds cause cell death by apoptosis and after 24 h, they increase the mean number of cells in programmed cell death, especially when treated with 2. In addition, the association with doxorubicin increases the apoptotic potential induced by tested compounds. Both isolates had effect on the reduction of the number of mitoses, especially when 2 at its highest concentration is associated with doxorubicin. CONCLUSIONS: Finally, these compounds are presented as potential agents in chemotherapy combined with doxorubicin, since they trigger the mechanism of apoptosis, which, through the mechanism of action of sesquiterpene lactones, leads to a reduction in toxicity. In addition, the tested compounds have the ability to exert a synergistic action with doxorubicin, possibly by down-regulating the drug resistance mechanisms.
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spelling pubmed-54924322017-06-30 Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin de Oliveira Mauro, Mariana Matuo, Renata de David, Natan Strapasson, Regiane Lauriano Batista Oliveira, Rodrigo Juliano Stefanello, Maria Élida Alves Kassuya, Cândida Aparecida Leite de Cepa Matos, Maria de Fátima Faria, Fábio José Carvalho Costa, Deiler Sampaio BMC Pharmacol Toxicol Research Article BACKGROUND: In order to obtain better clinical results in anticancer therapies, polychemotherapy or combination therapies are used. For this, the combinations are required to increase the efficacy and reduce the adverse reactions of the associated chemotherapies. The aim of this study was to evaluate the cytotoxic, apoptotic and (anti)proliferative potential of two sesquiterpene lactones isolated from Moquiniastrum polymorphum, 11,13-diidrozaluzanin C (1) and gochnatiolide C (2), and their associations with chemotherapeutic agents irinotecan, tamoxifen, cisplatin, 5-fluouracyl and doxorubicin in the tumoral lineage of MCF-7 breast adenocarcinoma. METHODS: The analyses were performed by MTT cytotoxicity assays, drug combination index (CI), apoptosis morphological assay and cell proliferation assay. Treatments were evaluated with short exposure times (4 h), followed or not by recovery in drug-free medium for 24 h. For the cell viability assay the statistical analysis was performed using software INSTAT, and the ANOVA/Tukey test was applied. Combination Indices (CI) was made using CompuSyn software and demonstrated through isoboles. The assays that evaluated cell death and proliferation used statistical analysis SAS 9.4 (Statistical Analysis System), and the procedure adopted was PROC NPAR1WAY. The Wilcoxon test at 5% level was applied for comparing statistical differences. RESULTS: The results demonstrated that the compounds decrease cell viability and increase their action when associated with irinotecan, tamoxifen and doxorubicin (CI < 1 and CI = 1). In periods of 4 h-exposure, the compounds cause cell death by apoptosis and after 24 h, they increase the mean number of cells in programmed cell death, especially when treated with 2. In addition, the association with doxorubicin increases the apoptotic potential induced by tested compounds. Both isolates had effect on the reduction of the number of mitoses, especially when 2 at its highest concentration is associated with doxorubicin. CONCLUSIONS: Finally, these compounds are presented as potential agents in chemotherapy combined with doxorubicin, since they trigger the mechanism of apoptosis, which, through the mechanism of action of sesquiterpene lactones, leads to a reduction in toxicity. In addition, the tested compounds have the ability to exert a synergistic action with doxorubicin, possibly by down-regulating the drug resistance mechanisms. BioMed Central 2017-06-29 /pmc/articles/PMC5492432/ /pubmed/28662728 http://dx.doi.org/10.1186/s40360-017-0156-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
de Oliveira Mauro, Mariana
Matuo, Renata
de David, Natan
Strapasson, Regiane Lauriano Batista
Oliveira, Rodrigo Juliano
Stefanello, Maria Élida Alves
Kassuya, Cândida Aparecida Leite
de Cepa Matos, Maria de Fátima
Faria, Fábio José Carvalho
Costa, Deiler Sampaio
Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin
title Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin
title_full Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin
title_fullStr Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin
title_full_unstemmed Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin
title_short Actions of sesquiterpene lactones isolated from Moquiniastrum polymorphum subsp. floccosum in MCF7 cell line and their potentiating action on doxorubicin
title_sort actions of sesquiterpene lactones isolated from moquiniastrum polymorphum subsp. floccosum in mcf7 cell line and their potentiating action on doxorubicin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5492432/
https://www.ncbi.nlm.nih.gov/pubmed/28662728
http://dx.doi.org/10.1186/s40360-017-0156-3
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