Apoptotic response to photodynamic therapy versus the Bcl-2 antagonist HA14-1.
In this study, murine leukemia L1210 cells were used to compare the effects of photodynamic therapy (PDT) with those of the apoptotic nonpeptidic Bcl-2 ligand ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (HA14-1). The photosensitizing agent capronyloxy-tetrakis methyloxyethyl porphycene (CPO) was selected from a group of sensitizers previously shown to target the antiapoptotic protein Bcl-2 for photodamage. Like PDT with CPO, HA14-1 caused the rapid activation of procaspase-3, followed by the appearance of an apoptotic morphology within 60 min. Caspase activation after a sublethal dose of either PDT or HA14-1 was enhanced by staurosporine or the bile acid ursodeoxycholic acid. Moreover, PDT promoted procaspase activation and lethality of HA14-1 and vice versa. Effects of PDT versus HA14-1 could not be distinguished on the basis of the reactive oxygen species formation. Both caused the rapid oxidation of 2',7'-dichlorofluorescein. These results are consistent with the hypothesis that Bcl-2 photodamage is a target for some photosensitizing agents.
Kessel
David
D
Department of Pharmacology, Wayne State University School of Medicine, Detroit MI 48201, USA. dhkessel@med.wayne.edu
Castelli
Michelle
M
Reiners
John J
JJ
D000818:Animals; D017209:Apoptosis; D001578:Benzopyrans / Q000494:pharmacology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D051379:Mice; D008856:Microscopy, Fluorescence; D009570:Nitriles / Q000494:pharmacology*; D010778:Photochemotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species; D019311:Staurosporine / Q000494:pharmacology
D001578:Benzopyrans; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine