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Robot technology identifies a Parkinsonian therapeutics repurpose to target stem cells of glioblastoma

Authors
  • Vargas-Toscano, Andres1
  • Khan, Dilaware1
  • Nickel, Ann-Christin1
  • Hewera, Michael1
  • Kamp, Marcel Alexander1
  • Fischer, Igor1
  • Steiger, Hans-Jakob1
  • Zhang, Wei2
  • Muhammad, Sajjad1
  • Hänggi, Daniel1
  • Kahlert, Ulf Dietrich1, 3, 2
  • 1 Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225, Germany
  • 2 Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100050, PR China
  • 3 German Consortium for Translational Cancer Research (DKTK), Essen/Düsseldorf, 45147, Germany
Type
Published Article
Journal
CNS Oncology
Publisher
Future Medicine
Publication Date
May 28, 2020
Volume
9
Issue
2
Identifiers
DOI: 10.2217/cns-2020-0004
PMID: 32462934
PMCID: PMC7341159
Source
PubMed Central
Keywords
License
Green

Abstract

Aim: Glioblastoma is a heterogeneous lethal disease, regulated by a stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells is a clinical need. Methodology: A robotic workstation was programmed to perform a drug concentration to cell-growth analysis on an in vitro model of glioblastoma stem cells (GSCs). Mode-of-action analysis of the selected top substance was performed with manual repetition assays and acquisition of further parameters. Results: We identified 22 therapeutic potential substances. Three suggested a repurpose potential of neurotransmitter signal-modulating agents to target GSCs, out of which the Parkinson's therapeutic trihexyphenidyl was most effective. Manual repetition assays and initial mode of action characterization revealed suppression of cell proliferation, cell cycle and survival. Conclusion: Anti-neurotransmitter signaling directed therapy has potential to target GSCs. We established a drug testing facility that is able to define a mid-scale chemo responsome of in vitro cancer models, possibly also suitable for other cell systems.

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