| Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231 cells. | |
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MedLine Citation:
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PMID: 20674353 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The resistance to methotrexate by a number of cancer cells such as breast cancer cell-line MDA-MB-231 due to poor permeability renders it less effective as an anticancer agent for these cells. Proline prodrug of methotrexate (Pro-MTX) was designed as a substrate of prolidase which is specific for imido bond of dipeptide containing proline and expected to penetrate MDA-MB-231 cells more efficiently. The prodrug was synthesized by solid-phase peptide synthesis method and examined as a substrate of pure prolidase as well as cell homogenate. The cytotoxicity against MDA-MB-231 and non-methotrexate resistant breast cancer cell line, MCF-7 was also examined by XTT assay. The results showed that Pro-MTX was a substrate of prolidase. It was also shown that the prodrug could be converted to parent drug methotrexate in Caco-2 and HeLa cell homogenate. When tested with Caco-2 and MCF-7 cells, Pro-MTX showed weaker cytotoxicity compared with methotrexate. But for methotrexate resistant MDA-MB-231 cells, Pro-MTX showed stronger activity than methotrexate. The results indicated that the proline prodrug of methotrexate may overcome the resistance of human breast cancer cells in culture. |
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Authors:
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Zhiqian Wu; Anandkumar Shah; Namrata Patel; Xudong Yuan |
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Publication Detail:
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Type: Journal Article Date: 2010-07-11 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 20 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-16 Completed Date: 2010-12-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 5108-12 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Division of Pharmaceutical Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, NY 11201, USA. james.wu@liu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antimetabolites, Antineoplastic
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pharmacology* Breast Neoplasms / pathology* Cell Line, Tumor Drug Resistance, Neoplasm* Humans Methotrexate / pharmacology* Prodrugs / pharmacology* Proline / chemistry* |
| Chemical | |
Reg. No./Substance:
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0/Antimetabolites, Antineoplastic; 0/Prodrugs; 147-85-3/Proline; 59-05-2/Methotrexate |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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