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Molecular Pharmacology

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Research ArticleArticle

Development of a Novel Nitro-Derivative of Noscapine for the Potential Treatment of Drug-Resistant Ovarian Cancer and T-Cell Lymphoma

Ritu Aneja, Surya N. Vangapandu, Manu Lopus, Ramesh Chandra, Dulal Panda and Harish C. Joshi
Molecular Pharmacology June 2006, 69 (6) 1801-1809; DOI: https://doi.org/10.1124/mol.105.021899
Ritu Aneja
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Surya N. Vangapandu
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Manu Lopus
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Ramesh Chandra
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Dulal Panda
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Harish C. Joshi
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This article has a correction. Please see:

  • Correction to “Development of a Novel Nitro-Derivative of Noscapine for the Potential Treatment of Drug-Resistant Ovarian Cancer and T-Cell Lymphoma” - August 01, 2007

Abstract

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.

  • Received December 20, 2005.
  • Accepted March 1, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 69 (6)
Molecular Pharmacology
Vol. 69, Issue 6
1 Jun 2006
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Research ArticleArticle

Development of a Novel Nitro-Derivative of Noscapine for the Potential Treatment of Drug-Resistant Ovarian Cancer and T-Cell Lymphoma

Ritu Aneja, Surya N. Vangapandu, Manu Lopus, Ramesh Chandra, Dulal Panda and Harish C. Joshi
Molecular Pharmacology June 1, 2006, 69 (6) 1801-1809; DOI: https://doi.org/10.1124/mol.105.021899

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Research ArticleArticle

Development of a Novel Nitro-Derivative of Noscapine for the Potential Treatment of Drug-Resistant Ovarian Cancer and T-Cell Lymphoma

Ritu Aneja, Surya N. Vangapandu, Manu Lopus, Ramesh Chandra, Dulal Panda and Harish C. Joshi
Molecular Pharmacology June 1, 2006, 69 (6) 1801-1809; DOI: https://doi.org/10.1124/mol.105.021899
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