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A Requirement for Bid for Induction of Apoptosis by Photodynamic Therapy with a Lysosome- but Not a Mitochondrion-targeted Photosensitizer |
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| Authors: | Song-mao Chiu Liang-yan Xue Minh Lam Myriam E Rodriguez Ping Zhang Malcolm E Kenney Anna-Liisa Nieminen Nancy L Oleinick |
| Institution: | 1. Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH;2. Department of Dermatology, Case Western Reserve University, Cleveland, OH
Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH;3. Department of Dermatology, Case Western Reserve University, Cleveland, OH;4. Department of Chemistry, Case Western Reserve University, Cleveland, OH;5. Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH Department of Chemistry, Case Western Reserve University, Cleveland, OH;6. Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, SC Hollings Cancer Center, Medical University of South Carolina, Charleston, SC |
| Abstract: | Photodynamic therapy (PDT) with lysosome-targeted photosensitizers induces the intrinsic pathway of apoptosis via the cleavage and activation of the BH3-only protein Bid by proteolytic enzymes released from photodisrupted lysosomes. To investigate the role of Bid in apoptosis induction and the role of damaged lysosomes on cell killing by lysosome-targeted PDT, we compared the responses of wild type and Bid-knock-out murine embryonic fibroblasts toward a mitochondrion/endoplasmic reticulum-binding photosensitizer, Pc 4, and a lysosome-targeted sensitizer, Pc 181. Whereas apoptosis and overall cell killing were induced equally well by Pc 4-PDT in both cell lines, Bid−/− cells were relatively resistant to induction of apoptosis and to overall killing following PDT with Pc 181, particularly at low PDT doses. Thus, Bid is critical for the induction of apoptosis caused by PDT with the lysosome-specific sensitizers, but dispensable for PDT targeted to other membranes. |
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