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
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Creator |
ANEJA, R
VANGAPANDU, SN LOPUS, M CHANDRA, R PANDA, D JOSHI, HC |
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Subject |
microtubule dynamics
living cells cem cells tubulin apoptosis mechanism mitosis agent polymerization suppression |
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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.
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Publisher |
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
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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 |
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Type |
Article
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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 |
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Language |
en
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