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.

Abstract

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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