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Development of a novel nitro-derivative of noscapine for the potential treatment of drug-resistant ovarian cancer and t-cell lymphoma

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Title Development of a novel nitro-derivative of noscapine for the potential treatment of drug-resistant ovarian cancer and t-cell lymphoma
 
Creator ANEJA, R
VANGAPANDU, SN
LOPUS, M
CHANDRA, R
PANDA, D
JOSHI, HC
 
Subject microtubule dynamics
living cells
cem cells
tubulin
apoptosis
mechanism
mitosis
agent
polymerization
suppression
 
Description 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 mu M 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.
 
Publisher AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
 
Date 2011-07-17T06:46:59Z
2011-12-26T12:50:09Z
2011-12-27T05:36:12Z
2011-07-17T06:46:59Z
2011-12-26T12:50:09Z
2011-12-27T05:36:12Z
2006
 
Type Article
 
Identifier MOLECULAR PHARMACOLOGY, 69(6), 1801-1809
0026-895X
http://dx.doi.org/10.1124/mol.105.021899
http://dspace.library.iitb.ac.in/xmlui/handle/10054/4643
http://hdl.handle.net/10054/4643
 
Language en