SHORT REPORT Nanoparticulate paclitaxel demonstrates antitumor activity in PC3 and Ace-1 aggressive prostate cancer cell lines 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 Received: 9 June 2013 /Accepted: 15 July 2013 /Published online: 13 September 2013 # Springer Science+Business Media New York 2013 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 nanopar- ticulate 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 pac- litaxel. Cell viability, apoptosis, and colony forming assays were analyzed and compared in the presence of both drugs. Microtubule structure was examined by fluorescence micros- copy 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 de- creasing 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. Keywords Animal models . Prostate cancer . Nanoparticle taxane . Chemotherapy Introduction Paclitaxel (PX), an antimitotic taxane, kills cancer cells by promoting microtubules to form polymers that stabilize there- by inhibiting microtubule disassembly [1, 2]. The end result is blocking mitotic progression, with arrest of cells in metaphase [1, 2]. The toxicity associated with PX, owing to solvents, limits its use. PX is not soluble in water, and is prepared with ethanol and polyethoxylated castor oil as solubilizing agents [2, 3]. These agents cause hypersensitivity reactions despite heavy premedication [3], and, as a result, several new types of PX are under investigation [4–8]. Nanoparticulate paclitaxel (nPX) formulation (CTI52010, Crititax®), is the least complex of these new formulations, and, following production, con- tains only pure paclitaxel in saline [9–11]. Prostate cancer is the most common malignancy in men, and castration-resistant prostatic cancer is responsible for the death of over 28,000 men yearly [12]. Chemotherapy plays an important role in the management of this incurable manifestation of the disease and taxanes, such as docetaxel and PX, are used as a single agent or in combination with other agents to treat castration-resistant prostatic cancer [13]. Work performed at The Comparative Oncology and Epigenetics Laboratory, Department of Veterinary Medicine and Surgery, University of Missouri S. M. Axiak-Bechtel (*) : S. R. Kumar : K. K. Dank : N. A. Clarkson : K. A. Selting : J. N. Bryan Comparative Oncology and Epigenetics Laboratory, Department of Veterinary Medicine and Surgery, University of Missouri, 900 East Campus Drive, Columbia, MO 65211, USA e-mail: bechtels@missouri.edu S. R. Kumar Harry S. Truman Veterans Hospital, Columbia, MO, USA T. J. Rosol Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210, USA J. Espinosa : C. J. Decedue CritiTech, Inc., 1849 E. 1450 Road, Lawrence, KS 66044, USA Invest New Drugs (2013) 31:1609–1615 DOI 10.1007/s10637-013-0006-0