5-ALA Photodynamic Therapy Induces Competing Death and Survival Pathways in Glioblastoma Cells
Julia Inglot1, Dorota Bartusik-Aebisher2, Joanna Katarzyna Strzelczyk3
1English Division Science Club, Faculty of Medicine, Collegium Medicum, University of Rzeszów, 35-310 Rzeszów, Poland.
Abstract:
Glioblastoma multiforme (GBM), isocitrate dehydrogenase (IDH)-wildtype, is the most aggressive primary malignant tumor of the central nervous system, characterized by poor prognosis and high recurrence rates despite standard multimodal treatment. This study investigates the molecular response of glioblastoma cells to 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT), focusing on gene expression changes associated with apoptosis, ferroptosis, and oxidative stress. Human glioblastoma T98G cells were treated with 5-ALA followed by light irradiation, and gene expression was analyzed using RT-qPCR. PDT induced moderate upregulation of pro-apoptotic genes (BAX, CASP3, FAS) alongside increased expression of the anti-apoptotic gene BCL2, indicating simultaneous activation of cell death and survival pathways. Ferroptosis-related genes showed mixed responses, with slight upregulation of ACSL4 and downregulation of GPX4, suggesting increased susceptibility to lipid peroxidation. The most significant change was observed in GCH1 expression, reflecting activation of oxidative stress response mechanisms. However, none of the observed changes reached statistical significance, likely due to the limited sample size. These findings demonstrate that PDT induces a complex and dual biological response in glioblastoma cells, involving both cytotoxic and adaptive mechanisms. This may limit therapeutic efficacy and contribute to treatment resistance. The results support the rationale for combining PDT with targeted molecular therapies aimed at inhibiting antioxidant defenses and anti-apoptotic pathways. Additionally, personalized therapeutic strategies based on tumor molecular profiles may enhance treatment outcomes. Further studies with larger sample sizes and functional validation are required to confirm these preliminary observations.
Insights
Photodynamic therapy (PDT) triggers complex responses in glioblastoma cells, activating both cell death and survival pathways. This dual effect may limit PDT efficacy, suggesting combination therapies for better outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Glioblastoma multiforme (GBM), IDH-wildtype, is a highly aggressive brain tumor with poor prognosis.
- Standard treatments for GBM often fail due to high recurrence rates and treatment resistance.
Purpose of the Study:
- To investigate the molecular effects of 5-aminolevulinic acid (5-ALA)-based photodynamic therapy (PDT) on glioblastoma cells.
- To analyze gene expression changes related to apoptosis, ferroptosis, and oxidative stress following PDT.
Main Methods:
- Human glioblastoma T98G cells were treated with 5-ALA and light irradiation.
- Gene expression analysis was performed using quantitative real-time PCR (RT-qPCR).
Main Results:
- PDT induced moderate upregulation of pro-apoptotic genes (BAX, CASP3, FAS) and the anti-apoptotic gene BCL2.
- Ferroptosis markers showed mixed responses (ACSL4 upregulated, GPX4 downregulated), indicating increased lipid peroxidation susceptibility.
- GCH1 expression, related to oxidative stress response, was notably altered, though not statistically significant.
Conclusions:
- PDT elicits a complex, dual biological response in glioblastoma cells, involving both cell death and survival mechanisms.
- This dual response may contribute to therapeutic resistance, highlighting the need for combination therapies.
- Targeting antioxidant defenses and anti-apoptotic pathways alongside PDT could enhance treatment efficacy.
