| Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells. | |
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MedLine Citation:
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PMID: 21553345 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Gliomas are the most common primary brain tumor, and their treatment is still a challenge. Here, we evaluated the antiproliferative effect of a novel combination of two potent oxidative stress enhancers: menadione (M) and sodium orthovanadate (SO). We observed both short-term and prolonged growth inhibitory effects of M or SO alone as well as in combination (M:SO) on DBTRG.05MG human glioma cells. A stronger antiproliferative effect was observed in the short-term proliferation assay with the M:SO combination compared to either investigated agent alone. In the long-term proliferation assay, a 10-day exposure to M:SO at concentrations of 10 μM:17.5 μM or 17.5 μM:10 μM was enough to kill 100% of the cells; no cell regrowth was observed after re-incubation in drug-free media. When used in combination, the single concentration of M and SO could be decreased by 2.5- to 5-fold of those used for each experimental drug alone and still obtain a similar antiproliferative effect. The underlying molecular mechanism was investigated by co-incubating M:SO with dithiothreitol (DTT) and genistein. Both substances partially neutralized the effects of the M:SO combination, showing additive effects. This observation suggests a role of oxidative stress and tyrosine kinase stimulation in the M:SO cytotoxic effect. Our results indicate that M:SO combination is an attractive alternative for glioma treatment that encourages further study. The neutralizing effects of genistein and DTT reveal a possibility for their use in the minimization of potential M:SO systemic toxicity. |
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Authors:
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Zahid M Delwar; Dimitrios Avramidis; Elna Follin; Yan Hua; Ake Siden; Mabel Cruz; Kajsa M Paulsson; Juan Sebastian Yakisich |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-10 |
Journal Detail:
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Title: Investigational new drugs Volume: - ISSN: 1573-0646 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8309330 Medline TA: Invest New Drugs Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Clinical Neuroscience R54, Karolinska Institute, Karolinska University Hospital, Huddinge, S-141 86, Stockholm, Sweden. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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