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

In English

Författare

  • Zahid M. Delwar
  • Dimitrios Avramidis
  • Elna Follin
  • Yan Hua
  • Ake Siden
  • Mabel Cruz
  • Kajsa M Paulsson
  • Juan Sebastian Yakisich

Summary, in English

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.

Publiceringsår

2012

Språk

Engelska

Sidor

1302-1310

Publikation/Tidskrift/Serie

Investigational New Drugs

Volym

30

Issue

4

Dokumenttyp

Artikel i tidskrift

Förlag

Springer

Ämne

  • Cancer and Oncology

Nyckelord

  • Gliomas
  • Menadione
  • Sodium orthovanadate
  • DTT
  • Genistein
  • Proliferation
  • Cytotoxicity

Status

Published

Forskningsgrupp

  • Antigen Presentation

ISBN/ISSN/Övrigt

  • ISSN: 0167-6997