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55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e. V. (DGNC)
1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

25. bis 28.04.2004, Köln

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Induction of cell death by the anti-malaria agent chloroquine in glioma cells

Chloroquin induziert den apoptotischen Zelltod in humanen Gliomzellen

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  • corresponding author Alf Giese - Department of Neurosurgery, University of Schleswig-Holstein, Campus Lübeck, Lübeck
  • E. Kim - Department of Neurosurgery, University of Schleswig-Holstein, Campus Lübeck, Lübeck
  • M. Brockmann - Department of Neuroradiology, University of Schleswig-Holstein, Campus Lübeck, Lübeck
  • E. Pawlak - Department of Neurosurgery, University of Schleswig-Holstein, Campus Lübeck, Lübeck
  • M. Ladehoff - Department of Neurosurgery, University of Schleswig-Holstein, Campus Lübeck, Lübeck

Deutsche Gesellschaft für Neurochirurgie. Ungarische Gesellschaft für Neurochirurgie. 55. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie e.V. (DGNC), 1. Joint Meeting mit der Ungarischen Gesellschaft für Neurochirurgie. Köln, 25.-28.04.2004. Düsseldorf, Köln: German Medical Science; 2004. DocMO.12.03

The electronic version of this article is the complete one and can be found online at: http://www.egms.de/en/meetings/dgnc2004/04dgnc0118.shtml

Published: April 23, 2004

© 2004 Giese et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

Text

Objective

Chloroquine has recently been shown to activate the ATM pathway, which regulates the tumoursuppressor gene p53 and induces cell death in different human cancer cells. We have investigated the effect of chloroquine treatment on cell death in cultured glioma cells and have established strategies using this compound in combined treatment with agents inducing apoptosis.

Methods

Seven established human glioma cell lines of known p53 status were treated with increasing concentrations of chloroquine to study the effect on cell growth, proliferation and colony formation. Cell death was determined using trypan blue exclusion, histone-complexed DNA fragmentation, DNA histograms and determination of the mitochondrial membrane potential.

Results

Chloroquine induces cell death in human glioma cells at a concentration as low as 5µM. The fraction of dead cells in treated population increases after two days following a single dose treatment reaching up to 80% at 20µM. Even though a range of chloroquine sensitivity was observed cell lines carrying a p53 mutation tended to be more sensitive to chloroquine treatment. In the course of chloroquine induced cell death no intracellular DNA fragmentation was observed. When chloroquine treatment was combined with drugs inducing apoptosis such as camptothecin, cell death was significantly increased.

Conclusions

We demonstrate, as a first report, that the orally available anti-malaria drug chloroquine is a potent inducer of cell death in human glioma cells. Chloroquine treatment sensitises glioma cells to drug induced apoptosis by agents such as camptothecin.