“In cancer, if you knock out one pathway, two others are there waiting to take over. With photodynamic therapy [PDT], you are knocking out pathways that cannot be replaced,” declared David Kessel, PhD, Professor, Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan. With more than 50 years of continuous research support from the National Institutes of Health to better understand the mechanisms and potential clinical applications of light-activated therapy, Dr. Kessel focuses here on a behind-the-scenes look at the subcellular environment after PDT. Featured topics of discussion include the mitochondrial and lysosomal pathways to cell death; the cell-protective and cell-destructive effects of autophagy; the good, the bad, and the ugly players in this biochemical arena, particularly singlet oxygen (the bad) and hydroxyl radicals (the ugly); and the photokilling benefits associated with targeting lysosomes.
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Kessel D, Vicente MG, Reiners JJ Jr. Initiation of apoptosis and autophagy by photodynamic therapy. Lasers Surg Med 2006;38:482–488.
Eskelinen EL. Doctor Jekyll and Mister Hyde: autophagy can promote both cell survival and cell death. Cell Death Differ 2005;12(Suppl 2):1468–1472.
Guillon-Munos A, van Bemmelen MX, Clarke PG. Role of phosphoinositide 3-kinase in the autophagic death of serum-deprived PC12 cells. Apoptosis 2005;10:1031–1041.
Donohue E, Tovey A, Vogl AW et al. . Inhibition of autophagosome formation by the benzoporphyrin derivative verteporfin. J Biol Chem 2011;286:7290–7300.
Price M, Terlecky SR, Kessel D. A role for hydrogen peroxide in the pro-apoptotic effects of photodynamic therapy. Photochem Photobiol 2009;85:1491–1496.
Ashur I, Goldschmidt R, Pinkas I et al. . Photocatalytic generation of oxygen radicals by the water-soluble bacteriochlorophyll derivative WST11, noncovalently bound to serum albumin. J Phys Chem A 2009;113:8027–8037.
Rodriguez ME, Zhang P, Azizuddin K et al. . Structural factors and mechanisms underlying the improved photodynamic cell killing with silicon phthalocyanine photosensitizers directed to lysosomes versus mitochondria. Photochem Photobiol 2009;85:1189–1200.