Document Detail


The effect of cellular environment and p53 status on the mode of action of the platinum derivative LA-12.
MedLine Citation:
PMID:  19499188     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we characterized the effects of LA-12 on tumor cell lines possessing wild type p53 and on p53-deficient/mutant cell lines and the results were compared to those obtained using cisplatin. We have determined changes of p53 levels, of its transcriptional activity, of its posttranscriptional modifications and the effect of the treatment on the cell cycle, on the induction of apoptosis and on gene expression. LA-12 induces weak accumulation of both transcriptionally active p53 tumor suppressor and of p21(WAF1/CIP1) protein. LA-12 and cisplatin also significantly differ in their effects on apoptosis and cell cycle and on gene expression spectra in studied cell lines. LA-12 induces higher apoptosis levels in comparison with those induced by cisplatin, especially in p53-deficient H1299 cells and in MCF-7DD cells with transcriptionally inactive p53. We suggest that LA-12-mediated apoptosis is not fully dependent on p53. This confirms the therapeutic potential of LA-12 as a more potent cytostatic agent for both tumor cells expressing wild type p53 and for p53-deficient or mutant cells.
Authors:
Eva Roubalová; Veronika Kvardová; Roman Hrstka; Sárka Borilová; Eva Michalová; Lenka Dubská; Petr Müller; Petr Sova; Borivoj Vojtesek
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-06-05
Journal Detail:
Title:  Investigational new drugs     Volume:  28     ISSN:  1573-0646     ISO Abbreviation:  Invest New Drugs     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-05-21     Completed Date:  2010-09-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  United States    
Other Details:
Languages:  eng     Pagination:  445-53     Citation Subset:  IM    
Affiliation:
Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Zlutý kopec 7, 656 53, Brno, Czech Republic.
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MeSH Terms
Descriptor/Qualifier:
Amantadine / analogs & derivatives*,  pharmacology
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Apoptosis Regulatory Proteins / metabolism
Cell Cycle / drug effects
Cell Line, Tumor
Cisplatin / pharmacology
Cyclin-Dependent Kinase Inhibitor p21 / metabolism
Gene Expression Regulation, Neoplastic / drug effects*
Genes, p53
Humans
Mutation
Organoplatinum Compounds / pharmacology*
Tumor Suppressor Protein p53 / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Organoplatinum Compounds; 0/Tumor Suppressor Protein p53; 0/bis(acetato)(1-adamantylamine)amminedichloroplatinum(IV); 15663-27-1/Cisplatin; 768-94-5/Amantadine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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