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Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells

Delwar, Zahid M. ; Avramidis, Dimitrios ; Follin, Elna LU ; Hua, Yan ; Siden, Ake ; Cruz, Mabel ; Paulsson, Kajsa M LU orcid and Yakisich, Juan Sebastian (2012) In Investigational New Drugs 30(4). p.1302-1310
Abstract
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 mu M:17.5 mu M or 17.5 mu M:10 mu M was enough to kill 100% of the cells; no cell regrowth was... (More)
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 mu M:17.5 mu M or 17.5 mu M:10 mu M 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. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Gliomas, Menadione, Sodium orthovanadate, DTT, Genistein, Proliferation, Cytotoxicity
in
Investigational New Drugs
volume
30
issue
4
pages
1302 - 1310
publisher
Springer
external identifiers
  • wos:000305955300003
  • scopus:84866734245
ISSN
0167-6997
DOI
10.1007/s10637-011-9680-y
language
English
LU publication?
yes
id
9b8a72a5-0111-4a16-9a6b-b563657bf5b4 (old id 3001343)
date added to LUP
2016-04-01 13:32:18
date last changed
2022-02-11 21:42:25
@article{9b8a72a5-0111-4a16-9a6b-b563657bf5b4,
  abstract     = {{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 mu M:17.5 mu M or 17.5 mu M:10 mu M 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.}},
  author       = {{Delwar, Zahid M. and Avramidis, Dimitrios and Follin, Elna and Hua, Yan and Siden, Ake and Cruz, Mabel and Paulsson, Kajsa M and Yakisich, Juan Sebastian}},
  issn         = {{0167-6997}},
  keywords     = {{Gliomas; Menadione; Sodium orthovanadate; DTT; Genistein; Proliferation; Cytotoxicity}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{1302--1310}},
  publisher    = {{Springer}},
  series       = {{Investigational New Drugs}},
  title        = {{Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells}},
  url          = {{http://dx.doi.org/10.1007/s10637-011-9680-y}},
  doi          = {{10.1007/s10637-011-9680-y}},
  volume       = {{30}},
  year         = {{2012}},
}