PT  - JOURNAL ARTICLE
AU  - Jun Zhou
AU  - Kamlesh Gupta
AU  - Shefali Aggarwal
AU  - Ritu Aneja
AU  - Ramesh Chandra
AU  - Dulal Panda
AU  - Harish C. Joshi
TI  - Brominated Derivatives of Noscapine Are Potent Microtubule-interfering Agents That Perturb Mitosis and Inhibit Cell Proliferation
AID  - 10.1124/mol.63.4.799
DP  - 2003 Apr 01
TA  - Molecular Pharmacology
PG  - 799--807
VI  - 63
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/63/4/799.short
4100  - http://molpharm.aspetjournals.org/content/63/4/799.full
SO  - Mol Pharmacol2003 Apr 01; 63
AB  - Noscapine, a microtubule-interfering agent, has been shown to arrest mitosis, to induce apoptosis, and to have potent antitumor activity. We report herein that two brominated derivatives of noscapine, 5-bromonoscapine (5-Br-nosc) and reduced 5-bromonoscapine (Rd 5-Br-nosc), have higher tubulin binding activity than noscapine and affect tubulin polymerization differently from noscapine. In addition, they are able to arrest cell cycle progression at mitosis at concentrations much lower than noscapine. Interestingly, whereas noscapine-arrested cells have nearly normal bipolar spindles, cells arrested by 5-Br-nosc and Rd 5-Br-nosc form multipolar spindles. Nevertheless, noscapine and the two derivatives all affect the attachment of chromosomes to spindle microtubules and they impair the tension across paired kinetochores to similar degrees. 5-Br-nosc and Rd 5-Br-nosc are also more active than noscapine in inhibiting the proliferation of various human cancer cells, including those that are resistant to paclitaxel and epothilone. Our results thus indicate a great potential for the use of 5-Br-nosc and Rd 5-Br-nosc both as biological tools for studying microtubule-mediated processes and as chemotherapeutic agents for the treatment of human cancers. The American Society for Pharmacology and Experimental Therapeutics