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Updated: Jun 29, 2026
07:49
Transmitochondrial Cybrid Generation Using Cancer Cell Lines
Published on: March 17, 2023
Mitochondrial DNA Content Modulates Chemosensitivity and Cellular Adaptation in Glioblastoma Cells
Siti Muslihah Ab Radzak1, Azim Patar1, Hsin-Chen Lee2
1Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, Kelantan, Malaysia.
The Eurasian Journal of Medicine
|June 27, 2026
Summary
Altering mitochondrial DNA (mtDNA) copy number impacts glioblastoma (GBM) cell response to chemotherapy. Restoring mtDNA levels enhances sensitivity to temozolomide, suggesting mtDNA as a therapeutic target for GBM drug resistance.
Area of Science:
- Oncology
- Cell Biology
- Genetics
Background:
- Mitochondrial DNA (mtDNA) copy number is linked to glioblastoma (GBM) progression and resistance to therapy.
- Understanding how mitochondrial content influences GBM cell chemosensitivity is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effect of altered mitochondrial DNA content on the in vitro chemotherapeutic response of glioblastoma cells.
- To explore the potential of modulating mtDNA levels as a strategy to overcome drug resistance in GBM.
Main Methods:
- Glioblastoma cell lines were treated to deplete and restore mitochondrial DNA (mtDNA).
- Real-time PCR quantified mtDNA levels, while CCK-8 assays measured cell viability.
- Wound healing, Transwell, and flow cytometry assays assessed migration, invasion, apoptosis, reactive oxygen species (ROS), and mitochondrial membrane potential (ΔΨm).
- Adenosine triphosphate (ATP) levels were quantified.
Main Results:
- Glioblastoma cells with depleted mtDNA showed increased mtDNA after temozolomide (TMZ) exposure but had reduced viability, migration, and invasion.
- These cells displayed adaptive responses indicating emerging resistance to TMZ.
- Restoration of mtDNA content led to recovery in all measured parameters, enhancing TMZ sensitivity.
Conclusions:
- Mitochondrial DNA content plays a critical role in modulating glioblastoma cell sensitivity to chemotherapy.
- Variations in mtDNA levels significantly influence cellular responses to chemotherapeutic agents like TMZ.
- mtDNA copy number may serve as a potential biomarker for GBM, and its modulation could be a viable strategy to combat drug resistance.
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