This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Iancu, C. Articles by Atweh, G. F. Search for Related Content PubMed PubMed Citation Articles by Iancu, C. Articles by Atweh, G. F.

Taxol and Anti-Stathmin Therapy: A Synergistic Combination that Targets the Mitotic Spindle¹

Departments of Medicine and Pediatrics, Mount Sinai School of Medicine, New York, New York 10029

Stathmin is an abundant cytosolic phosphoprotein that plays an important role in the regulation of cellular proliferation. Its major function is to promote depolymerization of the microtubules that make up the mitotic spindle. Taxol is an effective chemotherapeutic agent whose activity is mediated through stabilization of the microtubules of the mitotic spindle. We demonstrate that antisense inhibition of stathmin expression chemosensitizes K562 leukemic cells to the antitumor effects of Taxol and results in a synergistic inhibition of their growth and clonogenic potential. In the presence of stathmin inhibition, exposure to Taxol results in more severe mitotic abnormalities (hypodiploidy and multinucleation). This, in turn, results in increased apoptosis of the aneuploid cells during subsequent cell division cycles. This novel molecular-based therapeutic approach may provide an effective form of cancer therapy that would avoid the severe toxicities associated with the use of multiple chemotherapeutic agents with overlapping toxicity profiles.

This article has been cited by other articles:

				A.-L. Cheng, W.-G. Huang, Z.-C. Chen, F. Peng, P.-F. Zhang, M.-Y. Li, F. Li, J.-L. Li, C. Li, H. Yi, et al. Identification of Novel Nasopharyngeal Carcinoma Biomarkers by Laser Capture Microdissection and Proteomic Analysis Clin. Cancer Res., January 15, 2008; 14(2): 435 - 445. [Abstract] [Full Text] [PDF]

				E. Alli, J.-M. Yang, J. M. Ford, and W. N. Hait Reversal of Stathmin-Mediated Resistance to Paclitaxel and Vinblastine in Human Breast Carcinoma Cells Mol. Pharmacol., May 1, 2007; 71(5): 1233 - 1240. [Abstract] [Full Text] [PDF]

				S. J. Mistry and G. F. Atweh Therapeutic interactions between stathmin inhibition and chemotherapeutic agents in prostate cancer Mol. Cancer Ther., December 1, 2006; 5(12): 3248 - 3257. [Abstract] [Full Text] [PDF]

				S. J. Mistry, A. Bank, and G. F. Atweh Targeting stathmin in prostate cancer Mol. Cancer Ther., December 1, 2005; 4(12): 1821 - 1829. [Abstract] [Full Text] [PDF]

				Z. Liu, H. Lu, H. Shi, Y. Du, J. Yu, S. Gu, X. Chen, K. J. Liu, and C.-a. A. Hu PUMA Overexpression Induces Reactive Oxygen Species Generation and Proteasome-Mediated Stathmin Degradation in Colorectal Cancer Cells Cancer Res., March 1, 2005; 65(5): 1647 - 1654. [Abstract] [Full Text] [PDF]

				S. Don, N. M. Verrills, T. Y.E. Liaw, M. L.M. Liu, M. D. Norris, M. Haber, and M. Kavallaris Neuronal-associated microtubule proteins class III {beta}-tubulin and MAP2c in neuroblastoma: Role in resistance to microtubule-targeted drugs Mol. Cancer Ther., September 1, 2004; 3(9): 1137 - 1146. [Abstract] [Full Text] [PDF]

				K. Neben, A. Korshunov, A. Benner, G. Wrobel, M. Hahn, F. Kokocinski, A. Golanov, S. Joos, and P. Lichter Microarray-Based Screening for Molecular Markers in Medulloblastoma Revealed STK15 as Independent Predictor for Survival Cancer Res., May 1, 2004; 64(9): 3103 - 3111. [Abstract] [Full Text] [PDF]

				H. Miyashita, M. Kanemura, T. Yamazaki, M. Abe, and Y. Sato Vascular Endothelial Zinc Finger 1 Is Involved in the Regulation of Angiogenesis: Possible Contribution of Stathmin/OP18 as a Downstream Target Gene Arterioscler Thromb Vasc Biol, May 1, 2004; 24(5): 878 - 884. [Abstract] [Full Text]

				J.-G. Chen, C.-P. H. Yang, M. Cammer, and S. Band Horwitz Gene Expression and Mitotic Exit Induced by Microtubule-Stabilizing Drugs Cancer Res., November 15, 2003; 63(22): 7891 - 7899. [Abstract] [Full Text] [PDF]

				J. Asakuma, M. Sumitomo, T. Asano, T. Asano, and M. Hayakawa Selective Akt Inactivation and Tumor Necrosis Factor-related Apoptosis-inducing Ligand Sensitization of Renal Cancer Cells by Low Concentrations of Paclitaxel Cancer Res., March 15, 2003; 63(6): 1365 - 1370. [Abstract] [Full Text] [PDF]

				M. Takahashi, X. J. Yang, T. T. Lavery, K. A. Furge, B. O. Williams, M. Tretiakova, A. Montag, N. J. Vogelzang, G. G. Re, A. J. Garvin, et al. Gene Expression Profiling of Favorable Histology Wilms Tumors and Its Correlation with Clinical Features Cancer Res., November 15, 2002; 62(22): 6598 - 6605. [Abstract] [Full Text] [PDF]

				H. M. McDaid, S. Mani, H.-J. Shen, F. Muggia, D. Sonnichsen, and S. B. Horwitz Validation of the Pharmacodynamics of BMS-247550, an Analogue of Epothilone B, during a Phase I Clinical Study Clin. Cancer Res., July 1, 2002; 8(7): 2035 - 2043. [Abstract] [Full Text] [PDF]

				J.-G. Chen and S. B. Horwitz Differential Mitotic Responses to Microtubule-stabilizing and -destabilizing Drugs Cancer Res., April 1, 2002; 62(7): 1935 - 1938. [Abstract] [Full Text] [PDF]