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Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells.
MedLine Citation:
PMID:  21553345     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  JOURNAL ARTICLE     Date:  2011-5-10
Journal Detail:
Title:  Investigational new drugs     Volume:  -     ISSN:  1573-0646     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309330     Medline TA:  Invest New Drugs     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Clinical Neuroscience R54, Karolinska Institute, Karolinska University Hospital, Huddinge, S-141 86, Stockholm, Sweden.
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