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Molecular Biological Mechanisms in Photodynamic Therapy

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Photodynamic Therapy

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Abstract

Cellular and molecular photodamage mechanisms are initiated by light-activation of a photosensitizer following its accumulation in cellular targets. While lethal doses of photodynamic therapy (PDT) eliminate vessels and cells, sublethal effects occur, e.g., during fluorescence diagnosis (FD). Accordingly, the events subsequent photoactivation lead to different cellular endpoints being primarily growth stimulation, damage repair, autophagy, apoptosis, and necrosis. Activation of survival pathways seems to be not only involved in growth stimulation, but also in PDT damage transmission. Sublethal PDT results from activation of cellular damage protection and adaptive mechanisms, and can modulate signaling pathways and immune reactions. Autophagy may serve to rescue cells or lead to cell death under special conditions. Lethal PDT activates stress response, e.g., via mitochondria or ER, inducing apoptosis. If the damage is too severe, the cellular energy level low or the plasma membrane leaky, cells will die by necrosis.

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Abbreviations

AIF:

Apoptosis-inducing factor

AKT:

Protein kinase B

ALA:

Aminolevulinic acid

ANT:

Adenine nucleotide translocator

AP-1:

Activator protein 1

APAF-1:

Apoptotic protease activating factor-1

Bak:

Bcl-2 homologous antagonist/killer

Bax:

Bcl-2–associated X protein

BCL-2:

B-cell lymphoma 2

BID:

BH3 interacting-domain death agonist

COX-2:

Cyclooxygenase-2

DUSP-1:

Dual specificity phosphatase 1

ECM:

Extracellular matrix

ERK2:

Extracellular signal-regulated kinase 2

FAS:

TNF receptor superfamily, member 6

c-fos:

FBJ murine osteosarcoma viral oncogene homolog

FD:

Fluorescence diagnosis

HO-1:

Heme oxygenase 1

c-jun:

Jun proto-oncogene

JNK:

c-Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

mHK:

Mitochondria-bound hexokinase

mTOR:

Mammalian target of rapamycin

NF-kappa B:

Nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells

PDD:

Photodynamic diagnosis

PDT:

Photodynamic therapy

PI3 K:

Phosphatidylinositol-3-kinase

PpIX:

Protoporphyrin IX

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SERCA2:

Sarco/endoplasmic Ca2+ -ATPase-2

UPR:

Unfolded protein response

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Department of Molecular Biology, University of Salzburg, Salzburg, Austria

    Barbara Krammer & Thomas Verwanger

Authors
  1. Barbara Krammer
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  2. Thomas Verwanger
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Corresponding author

Correspondence to Barbara Krammer .

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Editors and Affiliations

  1. German University of Cairo, New Cairo City, Egypt

    Mahmoud H. Abdel-Kader

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Krammer, B., Verwanger, T. (2014). Molecular Biological Mechanisms in Photodynamic Therapy. In: Abdel-Kader, M. (eds) Photodynamic Therapy. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-39629-8_3

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