gms | German Medical Science

61st Annual Meeting of the German Society of Neurosurgery (DGNC) as part of the Neurowoche 2010
Joint Meeting with the Brazilian Society of Neurosurgery on the 20 September 2010

German Society of Neurosurgery (DGNC)

21 - 25 September 2010, Mannheim

Chloroquine inhibits growth of stem cell-like cells from malignant human brain tumors

Meeting Abstract

  • Jan Leppert - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany
  • Anja Kerstein - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany
  • Felix Kordowski - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany
  • Volker Tronnier - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany
  • Christina Zechel - Klinik für Neurochirurgie, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Germany

Deutsche Gesellschaft für Neurochirurgie. 61. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC) im Rahmen der Neurowoche 2010. Mannheim, 21.-25.09.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocP1720

DOI: 10.3205/10dgnc191, URN: urn:nbn:de:0183-10dgnc1916

Published: September 16, 2010

© 2010 Leppert 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

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Objective: Glioblastoma multiforme (GBM) is the most common primary central nervous tumor in adults making up approximately 50% of all primary intracranial tumors. They generally occur in the fifth and sixth decades of life. GBMs are infiltrating tumors located in the deep white matter or in the deep grey matter neighboring white matter. GBMs grow invasively, develop resistance to radiation and chemotherapy, and frequently recur. It has been proposed that a subpopulation of tumor cells with stem cell-like features (BTSC) mediates therapy resistance and regrowth. We isolated stem cell-like cells from several types of malignant brain tumors, determined marker expression, and investigated their responsiveness to drugs used in brain tumor therapy.

Methods: All primary cultures derived from malignant brain tumors encompassed neural stem cell-(NSC-)like cells, which exhibited self renewal. Growth behaviour and proliferation rate, however, differed largely. Dose curves showed that responsiveness to TMZ was significantly different between the various NSC-like cell lines, as BrdU incorporation was inhibited with different efficacy. Co-application of chloroquine (CQ), a drug used in the therapy of malaria enhanced responsiveness to TMZ in most NSC-like cell lines. Moreover, we could show, that 5µg/ml of CQ alone were already sufficient to strongly reduce BTSC growth. Since CQ-activity may induce autophagy in a p53-depending manner, we analyzed p53-expression by RT-PCR and western blot analysis.

Results: All BTSC cell lines expressed p53 mRNA. In contrast to the mRNA the protein expression levels differed largely. We assume that the effect of CQ on cell lines lacking p53 protein expression were significantly lower than on cell lines showing overexpression.

Conclusions: In summary our data indicate that the antimalarial drug chloroquine could reduce the growth of stem cell-like brain tumor cells and strengthen the responsiveness to an alkylating chemotherapeutic reagent, and thus may open to new ways in glioma therapy.