PT  - JOURNAL ARTICLE
AU  - Aneja, Ritu
AU  - Vangapandu, Surya N.
AU  - Lopus, Manu
AU  - Chandra, Ramesh
AU  - Panda, Dulal
AU  - Joshi, Harish C.
TI  - Development of a Novel Nitro-Derivative of Noscapine for the Potential Treatment of Drug-Resistant Ovarian Cancer and T-Cell Lymphoma
AID  - 10.1124/mol.105.021899
DP  - 2006 Jun 01
TA  - Molecular Pharmacology
PG  - 1801--1809
VI  - 69
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/69/6/1801.short
4100  - http://molpharm.aspetjournals.org/content/69/6/1801.full
SO  - Mol Pharmacol2006 Jun 01; 69
AB  - We have shown previously that an antitussive plant alkaloid, noscapine, binds tubulin, displays anticancer activity, and has a safe pharmacological profile in humans. Structure-function analyses pointed to a proton at position-9 of the isoquinoline ring that can be modified without compromising tubulin binding activity. Thus, many noscapine analogs with different functional moieties at position-9 were synthesized. Those analogs that kill human cancer cells resistant to other antimicrotubule agents, vincas and taxanes, were screened. Here, we present one such analog, 9-nitro-noscapine (9-nitro-nos), which binds tubulin and induces apoptosis selectively in tumor cells (ovarian and T-cell lymphoma) resistant to paclitaxel, vinblastine, and teniposide. 9-Nitro-nos treatment at doses as high as 100 μM did not affect the cell cycle profile of normal human fibroblasts. This selectivity of 9-nitro-nos for cancer cells represents a unique edge over the other available antimitotics. 9-Nitro-nos perturbs the progression of cell cycle by mitotic arrest, followed by apoptotic cell death associated with increased caspase-3 activation and appearance of terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells. Thus, we conclude that 9-nitro-nos has great potential to be a novel therapeutic agent for ovarian and T-cell lymphoma cancers, even those that have become drug-resistant to currently available chemotherapeutic drugs.