The role of the peripheral benzodiazepine receptor in the apoptotic response to photodynamic therapy.
Several previous studies have suggested that the peripheral benzodiazepine receptor (PBR) on the mitochondrial surface was an important target for photodynamic therapy (PDT). In this study we compared PBR affinity vs photodynamic efficacy of protoporphyrin-IX (PP-IX) and two structural analogs, PP-III and PP-XIII, using murine leukemia L1210 cells in culture. The results indicate that the three agents have approximately equal hydrophobicity, affinity for L1210 cells and ability to initiate photodamage leading to an apoptotic response. But only PP-IX had significant affinity for the PBR. These data indicate that the relationship between PDT efficacy and PBR affinity may hold only for sensitizers with the PP-IX configuration.
Kessel
D
D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA. dhkessel@med.wayne.edu
Antolovich
M
M
Smith
K M
KM
D000818:Animals; D017209:Apoptosis; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism; D011524:Protoporphyrins / Q000737:chemistry / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D011963:Receptors, GABA-A; C028025:protoporphyrin IX