Effect of Mitochondrial Fission Inhibition on Apoptosis in Glioblastoma Multiforme (GBM) Cells
Abstract
Aim: Glioblastoma multiforme (GBM) is characterized by poor prognosis and therapeutic resistance. Mitochondrial dynamics, particularly mitochondrial fission regulated by DRP1, play a critical role in apoptosis. This study aimed to investigate the effect of mitochondrial fission inhibition on apoptosis in U87 wild-type cells and to evaluate the potential synergistic therapeutic effect of combining mitochondrial fission inhibition with temozolomide (TMZ).
Materials and methods: The cytotoxic effects and IC₅₀ values of Mdivi-1 and TMZ were determined by a 72-hour MTT assay. Based on these results, 50 μM Mdivi-1 was selected for combination treatment with 50 μM TMZ, and the expression levels of DRP1, FIS1, BAX, and BCL2 were analyzed by qRT-PCR.
Results: Mitochondrial fission inhibition significantly reduced cell viability (p < 0.05). Combination treatment with Mdivi-1 and TMZ further decreased cell viability compared with the control group. qRT-PCR analysis revealed a significant decrease in BCL2 mRNA expression following Mdivi-1 treatment,
whereas changes in DRP1, FIS1, and BAX expression were not statistically significant.
Conclusion: These findings suggest that inhibition of mitochondrial fission may enhance the antiproliferative effect of TMZ in GBM cells. Targeting mitochondrial dynamics may represent a potential therapeutic strategy for overcoming treatment resistance; however, further studies are required to clarify the underlying molecular mechanisms.
Keywords
Glioblastoma, mitochondrial fission, apoptosis, temozolomide
Supporting Institution
Scientific Research Projects Coordination Unit (BAP), Ankara University (Project No: TYL-2022-2444)
Ethical Statement
The cells used in the study are commercially available so ethics committee approval is not required. The study protocol was appropriate in accordance with the Declaration of Helsinki.
Thanks
The authors would like to thank the Scientific Research Projects Coordination Unit (BAP) of Ankara University for financial support (Project No: TYL-2022-2444).
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