| Influence of ascorbic acid on the activity of the investigational anticancer drug KP1019. | |
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MedLine Citation:
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PMID: 21706338 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Ascorbic acid has been previously discussed to have antitumor potential through its interaction with transition metal ions such as iron and copper. Furthermore, ascorbic acid may act as a reducing agent for Ru(III) compounds such as indazolium trans-[tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019), an investigational anticancer drug which is supposed to be activated by reduction, prior to binding to cellular target proteins. Therefore, we investigated the influence of ascorbic acid on the activity of this antitumor metal complex in cell culture studies. We show that co-incubation of equicytotoxic, constant amounts of KP1019 with high concentrations of ascorbic acid (50-700 μM) increases cytotoxicity of the ruthenium anticancer drug in the human colon carcinoma cell line SW480, human cervical carcinoma KB-3-1 cells, and the multidrug-resistant subline KBC-1, whereas addition of low concentrations (2.7-50 μM) has a strong chemoprotective effect in the human colon carcinoma cell line SW480, but not in multidrug-resistant KBC-1 cells. Although cellular uptake of KP1019 is not altered, ascorbic acid induce stronger interaction of the ruthenium compound with DNA both in SW480 cells and under cell-free conditions with plasmid DNA. Even if DNA interactions probably play a subordinate role in vivo given the extensive protein binding of the compound, our data exemplify that ascorbic acid enhances the reactivity of KP1019 with biomolecules. Moreover, we demonstrate that the levels of KP1019-generated reactive oxygen species are markedly decreased by co-incubation with ascorbic acid. Conclusively, our results indicate that application of high doses of ascorbic acid might increase the anticancer effects of KP1019. |
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Authors:
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Caroline Bartel; Alexander E Egger; Michael A Jakupec; Petra Heffeter; Markus Galanski; Walter Berger; Bernhard K Keppler |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-26 |
Journal Detail:
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Title: Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry Volume: - ISSN: 1432-1327 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9616326 Medline TA: J Biol Inorg Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institute of Inorganic Chemistry, University of Vienna, Waehringer Strasse 42, 1090, Vienna, Austria. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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