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Nanoparticulate paclitaxel demonstrates antitumor activity in PC3 and Ace-1 aggressive prostate cancer cell lines

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Background Paclitaxel is an effective antimitotic agent in cancer treatment; however, one of its most common toxicities is hypersensitivity due to excipients used for water solubility. Nanoparticulate paclitaxel (Crititax®, CTI52010) is paclitaxel that consists only of nanoparticulate drug in saline. Our objective was to examine the effect of nanoparticulate paclitaxel on prostate cancer cells derived from castration-resistant prostate cancer in men and dogs, as companion dogs represent a unique naturally occurring model of castration-resistant prostate cancer. We hypothesized that nanoparticulate paclitaxel would be effective in affecting cell viability, colony forming ability, apoptosis, and induction of structural changes to the microtubules of prostate cancer cells. Methods Human PC3 and canine Ace-1 cells were treated with 0.001–1.0 μm concentrations of paclitaxel and nanoparticulate paclitaxel. Cell viability, apoptosis, and colony forming assays were analyzed and compared in the presence of both drugs. Microtubule structure was examined by fluorescence microscopy following incubation with drug. Results Nanoparticulate paclitaxel was as effective as standard paclitaxel in decreasing cell viability, decreasing colony forming ability, and inducing apoptosis in human and canine prostate cancer cells in a dose-dependent manner. Fluorescence microscopy confirmed the microtubule target of nanoparticulate paclitaxel. Conclusions Nanoparticulate paclitaxel is as effective as paclitaxel in decreasing cell viability, initiating apoptosis, decreasing cell survival, and causing rigidity of microtubules in both human and canine castration-resistant prostate cancer. This represents an attractive area for further study, using the companion dog as a model for disease in men.

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Acknowledgments

Nanoparticulate paclitaxel (CTI52010, Crititax®), was provided by CritiTech, Inc.

Disclosures

CD is Chief Scientific Officer and JE is Director of Laboratory Operations for CritiTech, Inc., manufacturer of Crititax®.

Grant support

This work was supported by a University of Missouri Phi Zeta grant.

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Authors and Affiliations

  1. Comparative Oncology and Epigenetics Laboratory, Department of Veterinary Medicine and Surgery, University of Missouri, 900 East Campus Drive, Columbia, MO, 65211, USA

    Sandra M. Axiak-Bechtel, Senthil R. Kumar, Kristin K. Dank, Nicole A. Clarkson, Kim A. Selting & Jeffrey N. Bryan

  2. Harry S. Truman Veterans Hospital, Columbia, MO, USA

    Senthil R. Kumar

  3. Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA

    Thomas J. Rosol

  4. CritiTech, Inc., 1849 E. 1450 Road, Lawrence, KS, 66044, USA

    Jahna Espinosa & Charles J. Decedue

Authors
  1. Sandra M. Axiak-Bechtel
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  2. Senthil R. Kumar
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  3. Kristin K. Dank
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  4. Nicole A. Clarkson
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  5. Kim A. Selting
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  6. Jeffrey N. Bryan
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  7. Thomas J. Rosol
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  8. Jahna Espinosa
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  9. Charles J. Decedue
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Corresponding author

Correspondence to Sandra M. Axiak-Bechtel.

Additional information

Work performed at The Comparative Oncology and Epigenetics Laboratory, Department of Veterinary Medicine and Surgery, University of Missouri

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Axiak-Bechtel, S.M., Kumar, S.R., Dank, K.K. et al. Nanoparticulate paclitaxel demonstrates antitumor activity in PC3 and Ace-1 aggressive prostate cancer cell lines. Invest New Drugs 31, 1609–1615 (2013). https://doi.org/10.1007/s10637-013-0006-0

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  • DOI: https://doi.org/10.1007/s10637-013-0006-0

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