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Cell Death Pathways in Photodynamic Therapy of Cancer
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA 02114, USA
Department of Dermatology, Harvard Medical School, Boston, MA 02114, USA
Boston University College of Engineering, Boston, MA 02114, USA
Harvard-MIT Division of Health Sciences and Technology, Cambridge, MA 02139, USA
* Author to whom correspondence should be addressed.
Received: 24 March 2011; in revised form: 26 April 2011 / Accepted: 3 May 2011 / Published: 3 June 2011
Abstract: Photodynamic therapy (PDT) is an emerging cancer therapy that uses the combination of non-toxic dyes or photosensitizers (PS) and harmless visible light to produce reactive oxygen species and destroy tumors. The PS can be localized in various organelles such as mitochondria, lysosomes, endoplasmic reticulum, Golgi apparatus and plasma membranes and this sub-cellular location governs much of the signaling that occurs after PDT. There is an acute stress response that leads to changes in calcium and lipid metabolism and causes the production of cytokines and stress response mediators. Enzymes (particularly protein kinases) are activated and transcription factors are expressed. Many of the cellular responses center on mitochondria and frequently lead to induction of apoptosis by the mitochondrial pathway involving caspase activation and release of cytochrome c. Certain specific proteins (such as Bcl-2) are damaged by PDT-induced oxidation thereby increasing apoptosis, and a build-up of oxidized proteins leads to an ER-stress response that may be increased by proteasome inhibition. Autophagy plays a role in either inhibiting or enhancing cell death after PDT.
Keywords: photodynamic therapy; cell death; apoptosis; necrosis; autophagy; cancer
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MDPI and ACS Style
Mroz, P.; Yaroslavsky, A.; Kharkwal, G.B.; Hamblin, M.R. Cell Death Pathways in Photodynamic Therapy of Cancer. Cancers 2011, 3, 2516-2539.
Mroz P, Yaroslavsky A, Kharkwal GB, Hamblin MR. Cell Death Pathways in Photodynamic Therapy of Cancer. Cancers. 2011; 3(2):2516-2539.
Mroz, Pawel; Yaroslavsky, Anastasia; Kharkwal, Gitika B; Hamblin, Michael R. 2011. "Cell Death Pathways in Photodynamic Therapy of Cancer." Cancers 3, no. 2: 2516-2539.