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Updated: Sep 20, 2026

An In Vitro Approach to Photodynamic Therapy
Published on: August 17, 2018
Role of p53 and ATM in photodynamic therapy-induced apoptosis
Viola Heinzelmann-Schwarz1, André Fedier, René Hornung
1Department of Obstetrics and Gynecology, Division of Gynecology, University Hospital of Zurich, 8091 Zurich, Switzerland.
Background And Objectives:
Photodynamic therapy (PDT) induces cell death through a laser light-activated photosensitizer and is a treatment option for tumors resistant to radio- and chemo-therapy.
Study Design/Materials And Methods:
We investigated whether m-THPC-PDT induces cell death by necrosis and/or apoptosis, and whether these responses are modulated by p53 and/or ATM, two cancer-associated genes. Sensitivity of atm(+/+)p53(+/+), atm(+/+)p53(-/-), and atm(-/-)p53(-/-) mouse embryonic fibroblasts to m-THPC-PDT performed at a wavelength of 652 nm was determined by the MTT assay, trypan blue-exclusion, and the TUNEL and caspase3-cleavage apoptosis assays. c-Abl protein level was determined by immunoblotting.
Results:
m-THPC-PDT rapidly induced cell death in a substantial fraction of cells by p53- and Ataxia telangiectasia mutated (ATM)-independent non-apoptotic processes. However, in the subset of apoptotic cells, apoptosis was reduced by loss of p53 and was even more reduced by the additional loss of ATM. Apoptosis correlated inversely with c-Abl level.
Conclusions:
p53 and ATM are not required for necrosis, but may be required for PDT-mediated apoptosis.
Insights
Photodynamic therapy (PDT) primarily causes cell death through necrosis, independent of p53 and ATM genes. However, these genes play a role in mediating apoptosis during PDT treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Photodynamic therapy (PDT) utilizes laser light-activated photosensitizers to induce cell death.
- PDT is a therapeutic option for radio- and chemo-resistant tumors.
Purpose of the Study:
- To investigate if m-THPC-PDT induces cell death via necrosis and/or apoptosis.
- To determine if p53 and ATM gene status modulate these cell death responses.
Main Methods:
- Utilized mouse embryonic fibroblasts with varying atm and p53 gene statuses (atm(+/+)p53(+/+), atm(+/+)p53(-/-), atm(-/-)p53(-/-)).
- Assessed cell death using MTT assay, trypan blue exclusion, TUNEL, and caspase-3 cleavage assays.
- Determined c-Abl protein levels via immunoblotting.
Main Results:
- m-THPC-PDT induced rapid, p53- and ATM-independent non-apoptotic cell death (necrosis).
- Apoptosis was reduced in cells lacking p53 and further reduced with the additional absence of ATM.
- Apoptosis levels showed an inverse correlation with c-Abl protein levels.
Conclusions:
- p53 and ATM are not essential for PDT-induced necrosis.
- p53 and ATM may play a role in facilitating PDT-mediated apoptosis.
- The findings suggest a complex interplay between gene status and cell death pathways in PDT response.
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