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Volume 48
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10.3390/cimb48070689
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

5-ALA Photodynamic Therapy Induces Competing Death and Survival Pathways in Glioblastoma Cells

by
Julia Inglot
1,
Dorota Bartusik-Aebisher
2,
Joanna Katarzyna Strzelczyk
3,
Angelika Myśliwiec
2,
Klaudia Dynarowicz
2,
Dorota Hudy
3,
Oliwia Trzaskoś
4,
Jacek Tabarkiewicz
4,
Aleksandra Kawczyk-Krupka
5,
Magdalena Moś
6 and
David Aebisher
7,*
1
English Division Science Club, Faculty of Medicine, Collegium Medicum, University of Rzeszów, 35-310 Rzeszów, Poland
2
Department of Biochemistry and General Chemistry, Faculty of Medicine, University of Rzeszów, 35-310 Rzeszów, Poland
3
Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 19 Jordana St., 41-808 Zabrze, Poland
4
Department of Human Immunology, Institute of Medical Sciences, Medical College of Rzeszów University, University of Rzeszow, 35-959 Rzeszów, Poland
5
Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
6
Department of Internal Diseases, Angiology and Physical Medicine, Center for Laser Diagnostics and Therapy, Medical University of Silesia, 41-902 Bytom, Poland
7
Department of Photomedicine and Physical Chemistry, Faculty of Medicine, University of Rzeszów, 35-959 Rzeszów, Poland
*
Author to whom correspondence should be addressed.
Curr. Issues Mol. Biol. 2026, 48(7), 689; https://doi.org/10.3390/cimb48070689
Submission received: 1 June 2026 / Revised: 25 June 2026 / Accepted: 29 June 2026 / Published: 3 July 2026
(This article belongs to the Special Issue Cancer-Associated Remodeling of Functional Molecular Pathways)
Versions Notes

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.
Keywords: glioblastoma multiforme (GBM); photodynamic therapy (PDT); 5-aminolevulinic acid (5-ALA); apoptosis; ferroptosis glioblastoma multiforme (GBM); photodynamic therapy (PDT); 5-aminolevulinic acid (5-ALA); apoptosis; ferroptosis

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MDPI and ACS Style

Inglot, J.; Bartusik-Aebisher, D.; Strzelczyk, J.K.; Myśliwiec, A.; Dynarowicz, K.; Hudy, D.; Trzaskoś, O.; Tabarkiewicz, J.; Kawczyk-Krupka, A.; Moś, M.; et al. 5-ALA Photodynamic Therapy Induces Competing Death and Survival Pathways in Glioblastoma Cells. Curr. Issues Mol. Biol. 2026, 48, 689. https://doi.org/10.3390/cimb48070689

AMA Style

Inglot J, Bartusik-Aebisher D, Strzelczyk JK, Myśliwiec A, Dynarowicz K, Hudy D, Trzaskoś O, Tabarkiewicz J, Kawczyk-Krupka A, Moś M, et al. 5-ALA Photodynamic Therapy Induces Competing Death and Survival Pathways in Glioblastoma Cells. Current Issues in Molecular Biology. 2026; 48(7):689. https://doi.org/10.3390/cimb48070689

Chicago/Turabian Style

Inglot, Julia, Dorota Bartusik-Aebisher, Joanna Katarzyna Strzelczyk, Angelika Myśliwiec, Klaudia Dynarowicz, Dorota Hudy, Oliwia Trzaskoś, Jacek Tabarkiewicz, Aleksandra Kawczyk-Krupka, Magdalena Moś, and et al. 2026. "5-ALA Photodynamic Therapy Induces Competing Death and Survival Pathways in Glioblastoma Cells" Current Issues in Molecular Biology 48, no. 7: 689. https://doi.org/10.3390/cimb48070689

APA Style

Inglot, J., Bartusik-Aebisher, D., Strzelczyk, J. K., Myśliwiec, A., Dynarowicz, K., Hudy, D., Trzaskoś, O., Tabarkiewicz, J., Kawczyk-Krupka, A., Moś, M., & Aebisher, D. (2026). 5-ALA Photodynamic Therapy Induces Competing Death and Survival Pathways in Glioblastoma Cells. Current Issues in Molecular Biology, 48(7), 689. https://doi.org/10.3390/cimb48070689

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