This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Landen, J. W. Articles by Archer, D. R. Search for Related Content PubMed PubMed Citation Articles by Landen, J. W. Articles by Archer, D. R.

Noscapine Crosses the Blood-Brain Barrier and Inhibits Glioblastoma Growth

Departments of ¹ Cell Biology, ² Neurology, ³ Pathology, ⁴ Neurosurgery, ⁵ Winship Cancer Institute, and ⁶ Hematology/Oncology, and ⁷ the AFLAC Cancer Center and Blood Disorder Service, Emory University School of Medicine, Atlanta, Georgia; and ⁸ University of Arizona, Department of Pharmacology, Tucson, Arizona

The opium alkaloid noscapine is a commonly used antitussive agent available in Europe, Asia, and South America. Although the mechanism by which it suppresses coughing is currently unknown, it is presumed to involve the central nervous system. In addition to its antitussive action, noscapine also binds to tubulin and alters microtubule dynamics in vitro and in vivo. In this study, we show that noscapine inhibits the proliferation of rat C6 glioma cells in vitro (IC₅₀ = 100 µM) and effectively crosses the blood-brain barrier at rates similar to the ones found for agents such as morphine and [Met]enkephalin that have potent central nervous system activity (P 0.05). Daily oral noscapine treatment (300 mg/kg) administered to immunodeficient mice having stereotactically implanted rat C6 glioblasoma into the striatum revealed a significant reduction of tumor volume (P 0.05). This was achieved with no identifiable toxicity to the duodenum, spleen, liver, or hematopoietic cells as determined by pathological microscopic examination of these tissues and flow cytometry. Furthermore, noscapine treatment resulted in little evidence of toxicity to dorsal root ganglia cultures as measured by inhibition of neurite outgrowth and yielded no evidence of peripheral neuropathy in animals. However, evidence of vasodilation was observed in noscapine-treated brain tissue. These unique properties of noscapine, including its ability to cross the blood-brain barrier, interfere with microtubule dynamics, arrest tumor cell division, reduce tumor growth, and minimally affect other dividing tissues and peripheral nerves, warrant additional investigation of its therapeutic potential.

This article has been cited by other articles:

				R. Aneja, M. Liu, C. Yates, J. Gao, X. Dong, B. Zhou, S. N. Vangapandu, J. Zhou, and H. C. Joshi Multidrug Resistance-Associated Protein-Overexpressing Teniposide-Resistant Human Lymphomas Undergo Apoptosis by a Tubulin-Binding Agent Cancer Res., March 1, 2008; 68(5): 1495 - 1503. [Abstract] [Full Text] [PDF]

				S. Assadian, A. Aliaga, R. F. Del Maestro, A. C. Evans, and B. J. Bedell FDG-PET imaging for the evaluation of antiglioma agents in a rat model Neuro-oncol, January 1, 2008; 10(3): 292 - 299. [Abstract] [Full Text] [PDF]

				P. Fanara, J. Banerjee, R. V. Hueck, M. R. Harper, M. Awada, H. Turner, K. H. Husted, R. Brandt, and M. K. Hellerstein Stabilization of Hyperdynamic Microtubules Is Neuroprotective in Amyotrophic Lateral Sclerosis J. Biol. Chem., August 10, 2007; 282(32): 23465 - 23472. [Abstract] [Full Text] [PDF]

				R. Aneja, J. Zhou, B. Zhou, R. Chandra, and H. C. Joshi Treatment of hormone-refractory breast cancer: apoptosis and regression of human tumors implanted in mice. Mol. Cancer Ther., September 1, 2006; 5(9): 2366 - 2377. [Abstract] [Full Text] [PDF]

				E. Vassal, C. Barette, X. Fonrose, R. Dupont, E. Sans-Soleilhac, and L. Lafanechere Miniaturization and Validation of a Sensitive Multiparametric Cell-Based Assay for the Concomitant Detection of Microtubule-Destabilizing and Microtubule-Stabilizing Agents J Biomol Screen, June 1, 2006; 11(4): 377 - 389. [Abstract] [PDF]

				R. Aneja, S. N. Vangapandu, M. Lopus, R. Chandra, D. Panda, and H. C. Joshi Development of a Novel Nitro-Derivative of Noscapine for the Potential Treatment of Drug-Resistant Ovarian Cancer and T-Cell Lymphoma Mol. Pharmacol., June 1, 2006; 69(6): 1801 - 1809. [Abstract] [Full Text] [PDF]

				R. Aneja, M. Lopus, J. Zhou, S. N. Vangapandu, A. Ghaleb, J. Yao, J. H. Nettles, B. Zhou, M. Gupta, D. Panda, et al. Rational Design of the Microtubule-Targeting Anti-Breast Cancer Drug EM015. Cancer Res., April 1, 2006; 66(7): 3782 - 3791. [Abstract] [Full Text] [PDF]

				R. Aneja, J. Zhou, S. N. Vangapandu, B. Zhou, R. Chandra, and H. C. Joshi Drug-resistant T-lymphoid tumors undergo apoptosis selectively in response to an antimicrotubule agent, EM011 Blood, March 15, 2006; 107(6): 2486 - 2492. [Abstract] [Full Text] [PDF]