Cytotoxic effect of menadione and sodium orthovanadate in combination on human glioma cells
(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:
https://lup.lub.lu.se/record/3001343
- author
- Delwar, Zahid M. ; Avramidis, Dimitrios ; Follin, Elna LU ; Hua, Yan ; Siden, Ake ; Cruz, Mabel ; Paulsson, Kajsa M LU and Yakisich, Juan Sebastian
- organization
- publishing date
- 2012
- 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}}, }