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Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model

The current first‐line treatment for advanced metastatic prostate cancer, i.e. docetaxel‐based therapy, is only marginally effective. The aim of the present study was to determine whether such therapy can be improved by combining docetaxel with Aneustat (OMN54), a multivalent botanical drug candidat...

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Autores principales: Qu, Sifeng, Wang, Kendric, Xue, Hui, Wang, Yuwei, Wu, Rebecca, Liu, Chengfei, Gao, Allen C., Gout, Peter W., Collins, Colin C., Wang, Yuzhuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528545/
https://www.ncbi.nlm.nih.gov/pubmed/24388358
http://dx.doi.org/10.1016/j.molonc.2013.12.004
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author Qu, Sifeng
Wang, Kendric
Xue, Hui
Wang, Yuwei
Wu, Rebecca
Liu, Chengfei
Gao, Allen C.
Gout, Peter W.
Collins, Colin C.
Wang, Yuzhuo
author_facet Qu, Sifeng
Wang, Kendric
Xue, Hui
Wang, Yuwei
Wu, Rebecca
Liu, Chengfei
Gao, Allen C.
Gout, Peter W.
Collins, Colin C.
Wang, Yuzhuo
author_sort Qu, Sifeng
collection PubMed
description The current first‐line treatment for advanced metastatic prostate cancer, i.e. docetaxel‐based therapy, is only marginally effective. The aim of the present study was to determine whether such therapy can be improved by combining docetaxel with Aneustat (OMN54), a multivalent botanical drug candidate shown to have anti‐prostate cancer activity in preliminary in vitro experiments, which is currently undergoing a Phase‐I Clinical Trial. Human metastatic, androgen‐independent C4‐2 prostate cancer cells and NOD‐SCID mice bearing PTEN‐deficient, metastatic and PSA‐secreting, patient‐derived subrenal capsule LTL‐313H prostate cancer tissue xenografts were treated with docetaxel and Aneustat, alone and in combination. In vitro, Aneustat markedly inhibited C4‐2 cell replication in a dose‐dependent manner. When Aneustat was combined with docetaxel, the growth inhibitions of the drugs were essentially additive. In vivo, however, the combination of docetaxel and Aneustat enhanced anti‐tumor activity synergistically and very markedly, without inducing major host toxicity. Complete growth inhibition and shrinkage of the xenografts could be obtained with the combined drugs as distinct from the drugs on their own. Analysis of the gene expression of the xenografts using microarray indicated that docetaxel + Aneustat led to expanded anticancer activity, in particular to targeting of cancer hallmarks that were not affected by the single drugs. Our findings, obtained with a highly clinically relevant prostate cancer model, suggest, for the first time, that docetaxel‐based therapy of advanced human prostate cancer may be improved by combining docetaxel with Aneustat.
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spelling pubmed-55285452017-08-15 Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model Qu, Sifeng Wang, Kendric Xue, Hui Wang, Yuwei Wu, Rebecca Liu, Chengfei Gao, Allen C. Gout, Peter W. Collins, Colin C. Wang, Yuzhuo Mol Oncol Research Articles The current first‐line treatment for advanced metastatic prostate cancer, i.e. docetaxel‐based therapy, is only marginally effective. The aim of the present study was to determine whether such therapy can be improved by combining docetaxel with Aneustat (OMN54), a multivalent botanical drug candidate shown to have anti‐prostate cancer activity in preliminary in vitro experiments, which is currently undergoing a Phase‐I Clinical Trial. Human metastatic, androgen‐independent C4‐2 prostate cancer cells and NOD‐SCID mice bearing PTEN‐deficient, metastatic and PSA‐secreting, patient‐derived subrenal capsule LTL‐313H prostate cancer tissue xenografts were treated with docetaxel and Aneustat, alone and in combination. In vitro, Aneustat markedly inhibited C4‐2 cell replication in a dose‐dependent manner. When Aneustat was combined with docetaxel, the growth inhibitions of the drugs were essentially additive. In vivo, however, the combination of docetaxel and Aneustat enhanced anti‐tumor activity synergistically and very markedly, without inducing major host toxicity. Complete growth inhibition and shrinkage of the xenografts could be obtained with the combined drugs as distinct from the drugs on their own. Analysis of the gene expression of the xenografts using microarray indicated that docetaxel + Aneustat led to expanded anticancer activity, in particular to targeting of cancer hallmarks that were not affected by the single drugs. Our findings, obtained with a highly clinically relevant prostate cancer model, suggest, for the first time, that docetaxel‐based therapy of advanced human prostate cancer may be improved by combining docetaxel with Aneustat. John Wiley and Sons Inc. 2013-12-15 2014-03 /pmc/articles/PMC5528545/ /pubmed/24388358 http://dx.doi.org/10.1016/j.molonc.2013.12.004 Text en © 2014 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Qu, Sifeng
Wang, Kendric
Xue, Hui
Wang, Yuwei
Wu, Rebecca
Liu, Chengfei
Gao, Allen C.
Gout, Peter W.
Collins, Colin C.
Wang, Yuzhuo
Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model
title Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model
title_full Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model
title_fullStr Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model
title_full_unstemmed Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model
title_short Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient‐derived, advanced prostate cancer tissue xenograft model
title_sort enhanced anticancer activity of a combination of docetaxel and aneustat (omn54) in a patient‐derived, advanced prostate cancer tissue xenograft model
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5528545/
https://www.ncbi.nlm.nih.gov/pubmed/24388358
http://dx.doi.org/10.1016/j.molonc.2013.12.004
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