Multiple components of photodynamic therapy can phosphorylate Akt

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.