Cytotoxic effects induced by docetaxel, gefitinib, and cyclopamine on side population and nonside population cell fractions from human invasive prostate cancer cells

Murielle Mimeault, Sonny L. Johansson, Jean Pierre Henichart, Patrick Depreux, Surinder Kumar Batra

Research output: Contribution to journalArticle

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Abstract

The present study has been undertaken to establish the therapeutic benefit of cotargeting epidermal growth factor receptor (EGFR) and sonic hedgehog pathways by using gefitinib and cyclopamine, respectively, for improving the efficacy of the current chemotherapeutic drug docetaxel to counteract the prostate cancer progression from locally invasive to metastatic and recurrent disease stages. The data from immuofluorescence analyses revealed that EGFR/Tyr1173-pEGFR, sonic hedgehog ligand, smoothened coreceptor, and GLI-1 were colocalized with the CD133+ stem cell-like marker in a small subpopulation of prostate cancer cells. These signaling molecules were also present in the bulk tumor mass of CD133- prostate cancer cells with a luminal phenotype detected in patient's adenocarcinoma tissues. Importantly, the results revealed that the CD133+/ CD44 high/AR-/low side population (SP) cell fraction endowed with a high self-renewal potential isolated from tumorigenic and invasive WPE1-NB26 cells by the Hoechst dye technique was insensitive to the current chemotherapeutic drug, docetaxel. In contrast, the docetaxel treatment induced significant antiproliferative and apoptotic effects on the CD133 -/CD44low/AR+ non-SP cell fraction isolated from the WPE1-NB26 cell line. Of therapeutic interest, the results have also indicated that combined docetaxel, gefitinib, and cyclopamine induced greater antiproliferative and apoptotic effects on SP and non-SP cell fractions isolated from WPE1-NB26 cells than individual drugs or two-drug combinations. Altogether, these observations suggest that EGFR and sonic hedgehog cascades may represent the potential therapeutic targets of great clinical interest to eradicate the total prostate cancer cell mass and improve the current docetaxel-based therapies against locally advanced and invasive prostate cancers, and thereby prevent metastases and disease relapse.

Original languageEnglish (US)
Pages (from-to)617-630
Number of pages14
JournalMolecular cancer therapeutics
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2010

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docetaxel
Prostatic Neoplasms
Population
Epidermal Growth Factor Receptor
Side-Population Cells
Pharmaceutical Preparations
Therapeutics
Drug Combinations
gefitinib
cyclopamine
Adenocarcinoma
Coloring Agents
Stem Cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Cytotoxic effects induced by docetaxel, gefitinib, and cyclopamine on side population and nonside population cell fractions from human invasive prostate cancer cells. / Mimeault, Murielle; Johansson, Sonny L.; Henichart, Jean Pierre; Depreux, Patrick; Batra, Surinder Kumar.

In: Molecular cancer therapeutics, Vol. 9, No. 3, 01.03.2010, p. 617-630.

Research output: Contribution to journalArticle

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