Robot technology identifies a Parkinsonian therapeutics repurpose to target stem cells of glioblastoma
Andres Vargas-Toscano1, Dilaware Khan1, Ann-Christin Nickel1
1Clinic for Neurosurgery, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225, Germany.
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.
Insights
Researchers identified trihexyphenidyl, a Parkinson's drug, as a potential glioblastoma stem cell (GSC) therapy. This anti-neurotransmitter approach effectively targets GSCs by inhibiting their proliferation and survival.
Area of Science:
- Neuroscience
- Oncology
- Pharmacology
Background:
- Glioblastoma is a deadly cancer driven by cancer stem cells and influenced by neurotransmitters.
- Targeting glioblastoma stem cells (GSCs) with novel chemotherapies is a critical clinical challenge.
Purpose of the Study:
- To identify novel chemotherapies targeting glioblastoma stem cells (GSCs).
- To investigate the potential of repurposing existing drugs, specifically neurotransmitter signal modulators, for GSC therapy.
Main Methods:
- Utilized a robotic workstation for high-throughput drug screening against an in vitro GSC model.
- Performed concentration-dependent cell growth analysis.
- Conducted mode-of-action studies on promising drug candidates.
Main Results:
- Identified 22 potential therapeutic substances.
- Discovered three neurotransmitter signal-modulating agents with repurposing potential against GSCs.
- Found trihexyphenidyl, a Parkinson's disease therapeutic, to be the most effective GSC-targeting agent.
- Demonstrated that trihexyphenidyl suppresses GSC proliferation, cell cycle progression, and survival.
Conclusions:
- Anti-neurotransmitter signaling therapies show promise for targeting glioblastoma stem cells (GSCs).
- Established a drug testing platform capable of defining the chemoresponsiveness of in vitro cancer models.
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