Intracellular signaling mechanisms in photodynamic therapy

Abstract

In photodynamic therapy (PDT) a sensitizer, light and oxygen are used to induce death of tumor cells and in the treatment of certain noncancerous conditions. Cell death in PDT may occur by apoptosis or by necrosis, depending on the sensitizer, on the PDT dose and on the cell genotype. Some sensitizers that have been used in PDT are accumulated in the mitochondria, and this may explain their efficiency in inducing apoptotic cell death, both in vitro and in vivo. In this review we will focus on the events that characterize apoptotic death in PDT and on the intracellular signaling events that are set in motion in photosensitized cells. Activation of phospholipases, changes in ceramide metabolism, a rise in the cytosolic free Ca 2 + concentration, stimulation of nitric oxide synthase (NOS), changes in protein phosphorylation and alterations in the activity of transcription factors and on gene expression have all been observed in PDT-treated cells. Although many of these metabolic reactions contribute to the demise process, some of them may antagonize cell death. Understanding the signaling mechanisms in PDT may provide means to modulate the PDT effects at the molecular level and potentiate its antitumor effectiveness. D

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

“…Even though the signal transduction after PDT mainly is triggered by the formation of singlet oxygen, cellular signalling after PDT is dependent on the photosensitizer, its localization, PDT-dose and also on the cell type used (Moor 2000, Almeida et al 2004, Uzdensky 2008. Several groups have shown an increasing interest in this field, and many different proteins and protein cascades have been investigated.…”

“…The JNK proteins are stress induced kinases (Vlahopoulos & Zoumpourlis 2004) shown to be activated by PDT with different photosensitizers (Almeida et al 2004). …”

Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles

“…Actually, the results of the in vivo use of PDT depend on the effect this therapy has on the tumor cells, on the vascular endothelial cells, and on the immune cells of the host. Combining these effects may lead to long-term control of the tumor (3).…”

“…Cell death following the application of PDT is either due to necrosis or apoptosis depending on the experimental model, the type or dose of PS, and the energy and wavelength of the light (3,4). Apoptosis is the dominant form of cell death in PDT because most of the PS accumulates in the mitochondrial membrane (5).…”

“…(1). Caspase-3 is the major effector in these pathways, www.bjournal.com.br Braz J Med Biol Res 44 (1) 2011 being responsible for the cleavage of the other caspases (-6, -7, -8) and finally for the cleavage of some nuclear proteins involved in DNA repair (3,6).…”