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01.12.2013 | SHORT REPORT | Ausgabe 6/2013

Investigational New Drugs 6/2013

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

Zeitschrift:
Investigational New Drugs > Ausgabe 6/2013
Autoren:
Sandra M. Axiak-Bechtel, Senthil R. Kumar, Kristin K. Dank, Nicole A. Clarkson, Kim A. Selting, Jeffrey N. Bryan, Thomas J. Rosol, Jahna Espinosa, Charles J. Decedue
Wichtige Hinweise
Work performed at The Comparative Oncology and Epigenetics Laboratory, Department of Veterinary Medicine and Surgery, University of Missouri

Summary

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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