Document Detail


Cytotoxic efficacy of a novel dinuclear platinum(II) complex in human breast cancer cells.
MedLine Citation:
PMID:  20598681     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Evaluation of the cytotoxicity of a novel dinuclear platinum(II) complex of formula Pt(2)(2-picoline)(4)(berenil)(2) employing a MTT assay and inhibition of [(3)H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that the complex was more of a potent antiproliferative agent than cisplatin. The DNA-binding ability of Pt(2)(2-picoline)(4)(berenil)(2) estimated by an ethidium displacement assay indicated that the complex showed strong specificity for AT base pairs in the minor groove of DNA. Our study showed that Pt(2)(2-picoline)(4)(berenil)(2) was a potent catalytic inhibitor of topoisomerase II in opposition to cisplatin. Pt(2)(2-picoline)(4)(berenil)(2) was found to be a more active inhibitor of collagen biosynthesis than cisplatin. The up regulation of beta(1)-integrin and insulin-like growth factor I (IGF-I) receptor expression by the complex was shown to be accompanied by an increase in the expression of mitogen activated protein kinases in breast cell lines. The phenomenon was related to the increased expression of nuclear factor-kappaB (NuF-kappaBeta) by Pt(2)(2-picoline)(4)(berenil)(2) as shown by the Western immunoblot analysis. Flow cytometric analysis and a fluorescent microscopy assay demonstrated that cell death appeared to result from apoptosis, with the possibility of secondary necrosis. The data presented suggested that Pt(2)(2-picoline)(4)(berenil)(2) impaired growth and metabolism of breast cancer cells more efficiently than cisplatin. These results indicated also the different properties of Pt(2)(2-picoline)(4)(berenil)(2) and cisplatin.
Authors:
Anna Bielawska; Bozena Popławska; Arkadiusz Surazyński; Robert Czarnomysy; Krzysztof Bielawski
Publication Detail:
Type:  Journal Article     Date:  2010-06-21
Journal Detail:
Title:  European journal of pharmacology     Volume:  643     ISSN:  1879-0712     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-07-26     Completed Date:  2010-12-07     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  34-41     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2010 Elsevier B.V. All rights reserved.
Affiliation:
Department of Medicinal Chemistry, Medical University of Białystok, Kilińskiego 1, 15-089 Białystok, Poland.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemistry,  pharmacology*
Apoptosis / drug effects*
Blotting, Western
Breast Neoplasms / metabolism,  pathology
Cell Culture Techniques
Cell Line, Tumor
Cell Proliferation / drug effects*
Cell Survival / drug effects
Collagen / biosynthesis
DNA / metabolism
Dose-Response Relationship, Drug
Electrophoresis, Polyacrylamide Gel
Female
Flow Cytometry
Humans
Immunoprecipitation
Microscopy, Fluorescence
Molecular Structure
Organoplatinum Compounds / chemistry,  pharmacology*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Organoplatinum Compounds; 9007-34-5/Collagen; 9007-49-2/DNA; 91080-16-9/calf thymus DNA

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