Porphyrin-mediated photosensitization - taking the apoptosis fast lane.
Photodynamic therapy (PDT), which is an approved anticancer treatment, is also an effective approach to treat certain immune-mediated (psoriasis), ocular (age-related macular degeneration) and cardiovascular (removal of atherosclerotic plaque and prevention of restenosis following angioplasty) conditions. PDT uses light-absorbing photosensitizers, often a porphyrin derivative, which accumulate somewhat selectively within proliferating cell types. Upon illumination with light of an activating wavelength, reactive oxygen species are produced in photosensitizer-containing cells. Cell death may ensue. PDT with various photosensitizers causes cells to die rapidly by apoptosis, a built-in suicide program during which the cell disassembles itself. This review considers the notable properties of photosensitizers that relate to their potent capacity to induce cell death upon photoactivation. Photosensitizers can trigger apoptosis by a direct action upon mitochondria, a feature enabling PDT to be an effective treatment for disease conditions in which anti-apoptotic mechanisms to standard chemotherapeutic agents are present. The contribution of cell signaling events to the photodynamic effect and the relationship of PDT to other apoptosis pathways are also considered. Uncovering the biochemistry of PDT-induced apoptosis fosters the identification of disease indications, as well as predicting the potential for the application of PDT in combination with other therapeutic agents.
Granville
D J
DJ
QLT PhotoTherapeutics Inc, Vancouver, British Columbia, V5T 4T5, Canada. dgranvil@qltinc.com
Hunt
D W
DW