| Differential processing of antitumour-active and antitumour-inactive trans platinum compounds by SKOV-3 ovarian cancer cells. | |
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MedLine Citation:
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PMID: 16765322 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In order to compare the mechanistic properties of the antitumour-active trans platinum complex trans-[PtCl(2){Z-HN=C(OMe)Me}(NH(3))] (trans-Z) and of the antitumour-inactive isomer of cisplatin trans-[PtCl(2)(NH(3))(2)] (trans-DDP), the differential processing of the two compounds by SKOV-3 ovarian cancer cells has been investigated. trans-Z and trans-DDP enter cells with the same efficacy, but trans-Z shows a two-fold higher affinity for cellular DNA. The treatment with trans-DDP IC(50) determines an initial and transient cytostatic effect, paralleled by a moderate increase of apoptosis and by sequential and reversible arrests in S and G(2)/M phases of cell-cycle. In contrast, trans-Z IC(50) determines an initial cytotoxic effect, a more persistent and marked increase of apoptosis, and a more marked and prolonged arrest in S and G(2)/M phases of the cell-cycle. Treatment-induced gene expression modifications indicate that phenotypic effects of trans-DDP are driven by an initial and transient up-regulation of some genes related to cell-cycle checkpoint and arrest networks, whereas the more dramatic phenotypic effects of trans-Z are driven by a persistent up-regulation of more numerous genes involved in cell-cycle checkpoint and arrest networks, and in genome stability and DNA repair. Therefore, molecular and cellular events have been identified which are produced by trans-Z but not by trans-DDP, and which likely represent the mechanistic basis of antitumour activity of trans-Z in the SKOV-3 system. |
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Authors:
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Angelina Boccarelli; Domenico Giordano; Giovanni Natile; Mauro Coluccia |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't Date: 2006-05-01 |
Journal Detail:
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Title: Biochemical pharmacology Volume: 72 ISSN: 0006-2952 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-10 Completed Date: 2006-08-30 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 280-92 Citation Subset: IM |
Affiliation:
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Department Biomedical Sciences and Human Oncology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / chemistry, toxicity* Apoptosis / genetics Cell Cycle / drug effects Cell Cycle Proteins / genetics Cell Line, Tumor Cell Proliferation / drug effects* Cell Survival / drug effects Cisplatin / chemistry, metabolism, toxicity* Cross-Linking Reagents / chemistry, toxicity DNA Fragmentation / drug effects DNA Repair / genetics Female Flow Cytometry Gene Expression Profiling Gene Expression Regulation, Neoplastic / drug effects Genomic Instability / genetics Inhibitory Concentration 50 Organoplatinum Compounds / chemistry, metabolism, toxicity* Ovarian Neoplasms / genetics, metabolism, pathology Stereoisomerism |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Cell Cycle Proteins; 0/Cross-Linking Reagents; 0/Organoplatinum Compounds; 0/dichlorobis(1-methoxyethanimine)platinum(II); 14913-33-8/transplatin; 15663-27-1/Cisplatin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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