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Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent
The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd(2)Spm); ii) the anti-proliferative activity of...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120851/ https://www.ncbi.nlm.nih.gov/pubmed/27880824 http://dx.doi.org/10.1371/journal.pone.0167218 |
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author | Batista de Carvalho, Ana L. M. Medeiros, Paula S. C. Costa, Francisco M. Ribeiro, Vanessa P. Sousa, Joana B. Diniz, Carmen Marques, Maria P. M. |
author_facet | Batista de Carvalho, Ana L. M. Medeiros, Paula S. C. Costa, Francisco M. Ribeiro, Vanessa P. Sousa, Joana B. Diniz, Carmen Marques, Maria P. M. |
author_sort | Batista de Carvalho, Ana L. M. |
collection | PubMed |
description | The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd(2)Spm); ii) the anti-proliferative activity of Pd(2)Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd(2)Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the Matrigel(TM) method and the SRB proliferation test. The results thus obtained evidence the ability of Pd(2)Spm to restrict angiogenesis and cell migration: Pd(2)Spm induced a marked inhibition of migration (43.8±12.2%), and a higher inhibition of angiogenesis (81.8±4.4% for total length values, at 4 μM) as compared to DTX at the clinical dosage 4x10(-2) μM (26.4±14.4%; n = 4 to 11). Combination of Pd(2)Spm/DTX was more effective as anti-invasive and anti-proliferative than DTX or Pd(2)Spm in sole administration, which is compatible with the occurrence of synergism: for the anti-angiogenic effect, IC(50(Pd2Spm/DTX)) = 0.5/0.5x10(-2) μM vs IC(50(DTX)) = 1.7x10(-2) μM and IC(50(Pd2Spm)) = 1.6 μM. In conclusion, the reported effects of Pd(2)Spm on angiogenesis, migration and proliferation showed that this compound is a promising therapeutic agent against this type of breast cancer. Moreover, combined administration of Pd(2)Spm and DTX was found to trigger a substantial synergetic effect regarding angiogenesis inhibition as well as anti-migratory and anti-proliferative activities reinforcing the putative use of Pd(II) complexes in chemotherapeutic regimens. This is a significant outcome, aiming at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials. |
format | Online Article Text |
id | pubmed-5120851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51208512016-12-15 Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent Batista de Carvalho, Ana L. M. Medeiros, Paula S. C. Costa, Francisco M. Ribeiro, Vanessa P. Sousa, Joana B. Diniz, Carmen Marques, Maria P. M. PLoS One Research Article The present work is aimed at evaluating the antitumour properties of a Pd(II) dinuclear complex with the biogenic polyamine spermine, by investigating: i) the anti-angiogenic and anti-migration properties of a Pd(II) dinuclear complex with spermine (Pd(2)Spm); ii) the anti-proliferative activity of Pd(2)Spm against a triple negative human breast carcinoma (MDA-MB-231); and finally iii) the putative interaction mediated by combination of Pd(2)Spm with Docetaxel. Anti-invasive (anti-angiogenic and anti-migratory) as well as anti-proliferative capacities were assessed, for different combination schemes and drug exposure times, using the CAM assay and VEGFR2 activity measurement, the Matrigel(TM) method and the SRB proliferation test. The results thus obtained evidence the ability of Pd(2)Spm to restrict angiogenesis and cell migration: Pd(2)Spm induced a marked inhibition of migration (43.8±12.2%), and a higher inhibition of angiogenesis (81.8±4.4% for total length values, at 4 μM) as compared to DTX at the clinical dosage 4x10(-2) μM (26.4±14.4%; n = 4 to 11). Combination of Pd(2)Spm/DTX was more effective as anti-invasive and anti-proliferative than DTX or Pd(2)Spm in sole administration, which is compatible with the occurrence of synergism: for the anti-angiogenic effect, IC(50(Pd2Spm/DTX)) = 0.5/0.5x10(-2) μM vs IC(50(DTX)) = 1.7x10(-2) μM and IC(50(Pd2Spm)) = 1.6 μM. In conclusion, the reported effects of Pd(2)Spm on angiogenesis, migration and proliferation showed that this compound is a promising therapeutic agent against this type of breast cancer. Moreover, combined administration of Pd(2)Spm and DTX was found to trigger a substantial synergetic effect regarding angiogenesis inhibition as well as anti-migratory and anti-proliferative activities reinforcing the putative use of Pd(II) complexes in chemotherapeutic regimens. This is a significant outcome, aiming at the application of these combined strategies towards metastatic breast cancer (or other type of resistant cancers), justifying further studies that include pre-clinical trials. Public Library of Science 2016-11-23 /pmc/articles/PMC5120851/ /pubmed/27880824 http://dx.doi.org/10.1371/journal.pone.0167218 Text en © 2016 Batista de Carvalho et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Batista de Carvalho, Ana L. M. Medeiros, Paula S. C. Costa, Francisco M. Ribeiro, Vanessa P. Sousa, Joana B. Diniz, Carmen Marques, Maria P. M. Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent |
title | Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent |
title_full | Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent |
title_fullStr | Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent |
title_full_unstemmed | Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent |
title_short | Anti-Invasive and Anti-Proliferative Synergism between Docetaxel and a Polynuclear Pd-Spermine Agent |
title_sort | anti-invasive and anti-proliferative synergism between docetaxel and a polynuclear pd-spermine agent |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120851/ https://www.ncbi.nlm.nih.gov/pubmed/27880824 http://dx.doi.org/10.1371/journal.pone.0167218 |
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