Advanced

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 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)
Please use this url to cite or link to this publication:
author
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
2012-09-03 07:19:07
date last changed
2017-01-01 05:43:37
@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},
  keyword      = {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},
  volume       = {30},
  year         = {2012},
}