Multiple Components of Photodynamic Therapy Can Phosphorylate Akt^†

Abstract

A growing number of clinically relevant molecular and cellular responses are observed following photodynamic therapy (PDT). PDT-mediated oxidative stress and PDT-induced tissue hypoxia can elicit the transcriptional and/or translational expression of genes associated with cellular stress, inflammation, angiogenesis, immuno-modulation, apoptosis and signal transduction. One of the signaling molecules activated by oxidative stress is Akt/protein kinase B. Phosphorylation of Akt/protein kinase B activates this signaling molecule and induces a survival response in effected cells and tissue. We hypothesized that PDT using Photofrin (PH) as the photosensitizer could also induce increased levels of Akt phosphorylation. Results from our initial set of experiments demonstrated that in vitro and in vivo PDT treatments induced Akt phosphorylation. Interestingly, incubation of mouse and human breast cancer cells with the porphyrin-based photosensitizer, PH, increased the expression of Akt phosphorylation in the absence of light. Exposure of the corresponding mouse and human-derived breast cancer tumors growing in mice to 630 nm light in the absence of PH administration also induced Akt phosphorylation. These results demonstrate that individual components of the PDT process, photosensitizer alone and light alone, as well as the complete PDT procedure can activate the Akt signaling pathway.

On the Role of Phosphatidylinositol 3-Kinase, Protein Kinase B/Akt, and Glycogen Synthase Kinase-3β in Photodynamic Injury of Crayfish Neurons and Glial Cells

“…Likewise, inhibition of Akt did not influence PDT-induced elimination of neuronal activity and apoptosis of glial cells indicating that Akt was not involved in the protection of glial cells from PDT-induced apoptosis and in the regulation of neuron firing. These results were not in agreement with the data on the protective role of the PI3K/Akt pathway in photosensitized mammalian cells, in which PDT not only induced apoptosis but also initiated PI3K/Akt-related pro-survival pathways (Xue et al 1999;Zhuang and Kochevar 2003;Schieke et al 2004;Volanti et al 2005;Bozkulak et al 2007;Kocanova et al 2007;Zheng et al 2008;Espada et al 2009;Ferrario and Gomer 2010). The nonparticipation of PI3K and Akt in the regulation of glial apoptosis was, possibly, a specific feature of the crayfish nervous system.…”

“…The signaling pathway involving phosphatidylinositol 3-kinase (PI3K), protein kinase B/Akt (Akt), and glycogen synthase kinase-3β (GSK-3β) plays usually the protective, anti-apoptotic role (Krasilnikov 2000;Duronio 2008). Along with induction of necrosis and apoptosis, PDT is known to activate the protective PI3K/Akt pathway in diverse cell lines (Xue et al 1999;Zhuang and Kochevar 2003;Schieke et al 2004;Bozkulak et al 2007;Espada et al 2009). However, the role of downstream enzymes such as GSK-3β in photodynamic cell damage, particularly in nerve tissue injury, has not been studied yet.…”

The effect of photodynamic therapy on tumor angiogenesis

“…Our earlier investigation proved that nasopharyngeal cells maintained in hypoxic condition induce the expression of the PDGF-b gene whereas upregulation of HIF-1a was observed both in hypoxic and normoxic environment [30]. Interestingly, Buzkulok et al [64] demonstrated that individual components of the PDT process, photosensitizer alone and light alone as well as the complete PDT procedure, could activate the Akt signaling pathway in murine and human breast cancer cells and tumors. Wei et al [65] demonstrated in epithelial tumor cells that while the action of IL-6 cytokines through their membrane receptors is attenuated, regulation by IL-6 via trans-signalling is established, thus enhancing PDT.…”

“…In a recent study, the same group also demonstrated that Akt phosphorylation was induced by multiple PDT components in in vitro and in vivo treatments. Additionally, they demonstrated that blockage of Akt phosphorylation using P13-K inhibitors can increase PDT-mediated apoptosis within treated cells [64].…”

Combined Exposure to Electrochemical Lysis and Photodynamic Therapy

“…The potentialities of modern oncology were essentially extended with the development of photodynamic therapy (PDT), a modern organ-sparing therapeutic method, based on selective laser exposure of tumor tissues and cells pre-sensitized by a tumorotropic stain [4,5]. However, despite the progress in development of this method, relapses sometimes emerge after therapy [6], and hence, combination of PDT with other methods used for cancer treatment seems to be a promising trend. One of these methods, though little studied by the present time, is electrochemical lysis (ECL).…”