Photodynamic therapy: shedding light on the biochemical pathways regulating porphyrin-mediated cell death

Photodynamic therapy (PDT) is a clinically approved treatment for the ocular condition age-related macular degeneration, and certain types of cancer. PDT is also under investigation for other ocular, as well as, immune-mediated and cardiovascular indications. PDT is a two step procedure. In the first step, the photosensitizer, usually a porphyrin derivative, is administered and taken up by cells. The second step involves activation of the photosensitizer with a specific wavelength of visible light. Exposure to light of an activating wavelength generates reactive oxygen species within cells containing photosensitizer. PDT with porphyrin photosensitizers induces rapid apoptotic cell death, an event which may be attributed to the close association of these compounds with mitochondria. Thus, PDT is an attractive method to treat ailments such as cancer, viral infections, autoimmune disorders and certain cardiovascular diseases in which the apoptotic program may be compromised. The present review examines the cellular events triggered at lethal and sublethal PDT doses and their relationship to the subsequent effects exerted upon cells.