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

Sifeng Qu, Kendric Wang, Hui Xue, Yuwei Wang, Rebecca Wu, Chengfei Liu, Allen C Gao, Peter W. Gout, Colin C. Collins, Yuzhuo Wang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 invitro 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. Invitro, 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. Invivo, 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.

Original languageEnglish (US)
Pages (from-to)311-322
Number of pages12
JournalMolecular Oncology
Volume8
Issue number2
DOIs
StatePublished - Mar 2014

Fingerprint

docetaxel
Heterografts
Prostatic Neoplasms
Pharmaceutical Preparations
Inbred NOD Mouse
Clinical Trials, Phase I
SCID Mice
Therapeutics
Growth
Androgens
Capsules

Keywords

  • Advanced prostate cancer
  • Aneustat
  • Docetaxel
  • Microarray
  • OMN54

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Medicine

Cite this

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.

In: Molecular Oncology, Vol. 8, No. 2, 03.2014, p. 311-322.

Research output: Contribution to journalArticle

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. In: Molecular Oncology. 2014 ; Vol. 8, No. 2. pp. 311-322.
@article{c8c0c972cdd041028944a6c2685070f2,
title = "Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient-derived, advanced prostate cancer tissue xenograft model",
abstract = "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 invitro 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. Invitro, 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. Invivo, 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.",
keywords = "Advanced prostate cancer, Aneustat, Docetaxel, Microarray, OMN54",
author = "Sifeng Qu and Kendric Wang and Hui Xue and Yuwei Wang and Rebecca Wu and Chengfei Liu and Gao, {Allen C} and Gout, {Peter W.} and Collins, {Colin C.} and Yuzhuo Wang",
year = "2014",
month = "3",
doi = "10.1016/j.molonc.2013.12.004",
language = "English (US)",
volume = "8",
pages = "311--322",
journal = "Molecular Oncology",
issn = "1574-7891",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Enhanced anticancer activity of a combination of docetaxel and Aneustat (OMN54) in a patient-derived, advanced prostate cancer tissue xenograft model

AU - Qu, Sifeng

AU - Wang, Kendric

AU - Xue, Hui

AU - Wang, Yuwei

AU - Wu, Rebecca

AU - Liu, Chengfei

AU - Gao, Allen C

AU - Gout, Peter W.

AU - Collins, Colin C.

AU - Wang, Yuzhuo

PY - 2014/3

Y1 - 2014/3

N2 - 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 invitro 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. Invitro, 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. Invivo, 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.

AB - 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 invitro 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. Invitro, 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. Invivo, 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.

KW - Advanced prostate cancer

KW - Aneustat

KW - Docetaxel

KW - Microarray

KW - OMN54

UR - http://www.scopus.com/inward/record.url?scp=84894293446&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894293446&partnerID=8YFLogxK

U2 - 10.1016/j.molonc.2013.12.004

DO - 10.1016/j.molonc.2013.12.004

M3 - Article

C2 - 24388358

AN - SCOPUS:84894293446

VL - 8

SP - 311

EP - 322

JO - Molecular Oncology

JF - Molecular Oncology

SN - 1574-7891

IS - 2

ER -