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73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

29.05. - 01.06.2022, Köln

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The antineoplastic effect of antiepileptic drugs in patient-derived IDH mutant glioma stem cells

Antineoplastische Wirkung von Antiepileptika in IDH mutierten Gliomstammzellen

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  • presenting/speaker Huy Philip Dao Trong - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Gerhard Jungwirth - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Rolf Warta - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Andreas W. Unterberg - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland
  • Christel Herold-Mende - Universitätsklinikum Heidelberg, Neurochirurgische Klinik, Heidelberg, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 73. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Griechischen Gesellschaft für Neurochirurgie. Köln, 29.05.-01.06.2022. Düsseldorf: German Medical Science GMS Publishing House; 2022. DocP051

doi: 10.3205/22dgnc363, urn:nbn:de:0183-22dgnc3639

Published: May 25, 2022

© 2022 Dao Trong et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: Patients diagnosed with an IDH mutant glioma suffer more frequently from epilepsy than other brain tumor patients. This is especially concerning because recent discoveries showed that epileptic activity can promote tumor proliferation. Antiepileptic drugs might be able to interfere in these signaling pathways and lead to growth inhibition. In this study we tested 20 antiepileptic drugs (AEDs) in 6 well established IDH mutant glioma stem cell lines for an antineoplastic effect.

Methods: For the initial drug screen, we resuspended our spheroid cultures to a single cell suspension and treated the cells the day after with 20 AEDs for a duration of 72h. Cell vitality was measured using the “CellTiterGlo 3D” assay (Promega). After the identification of antiproliferative AEDs, the maximal half inhibitory concentration (IC50) was established with a dilution series of the candidate drug. Apoptosis assays were performed using the “Caspase 3/7 Glo” assay (Promega). Spheroid growth and vitality were measured using the “live/dead” fluorescence staining (Invitrogen).

Results: The initial drug screen identified one effective antiepileptic drug, which showed an IC50 below 39µM in 4/6 cell lines (mean 31.5µM; 17,4 - 39.0 µM). The treated tumor spheroids showed a significant growth inhibition compared to the DMSO control spheroids (mean volume 7.3nl SD 5nl vs. 2.3nl SD 2nl; p=0.005). The Caspase 3/7 assay was able to show that the rate of apoptosis of treated cells was elevated to up to 50%.

Conclusion: The drug screen of 20 antiepileptic drugs with 6 patient derived IDH mutated glioma stem cell lines was able to identify one antineoplastic antiepileptic drug. This could serve as a basis to integrate the antiepileptic drug into established chemotherapies to look for possible synergies.