Delivery Systems and Methods for Nocapine and Noscapine Derivatives, Useful as Anticancer Agents

Emory University
posted on 07/23/2010

• request more info 
•   
•  LICENSE ONLINE

Applications

Can be used for the treatment of neoplastic disease

Summary

A variety of chemotherapeutic agents interact with tubulin, the major protein of mitotic spindles, resulting in mitotic arrest and ultimately cell death in rapidly dividing cells. Athough tubulin-targeting agents are capable of arresting cells in mitotis, these drugs indiscriminantly target both neoplastic and healthy cells resulting in toxic side effects. Thus, there is an urgent need to direct research efforts towards developing more specific chemotherapeutic agents.

The Joshi laboratory has identified noscapiane, an opium alkaloid, which arrests a variety of tumor cells in mitosis. Cough suppression was the only pronounced pharmacologic effect of noscapine known for over thirty years until the Joshi lab demonstrated that noscapine: 1) binds to tubulin and alters its conformation and assembly properties; 2) interferes with microtubule dynamics both in vitro and in living cells; 3) arrests a variety of mammalian cells in mitosis and targets them for apoptosis; and 4) oral administration inhibits the growth of murine thymoma, human breast, bladder, and melanoma tumor cells, and murine and human gliolbastoma cells by inducing polyploidy and apoptosis.

In contrast to other microtubule interacting agents such as paclitaxel, nocodazole, and vinblastine, noscapine modifies microtubule dynamics without affecting total tubulin polymer mass in reconstituted systems and without altering the steady-state monomer/polymer equilibrium of microtubule assembly in cells.  In addition, noscapine does not appear to cause the toxic side effects associated with other microtubule targeting agents such as alopecia, diarrhea, nausea, and peripheral neuropathy.