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Apoptotic Response to Photodynamic Therapy versus the Bcl‐2 Antagonist HA14‐1 ¶
Author(s) -
Kessel David,
Reiners John J.
Publication year - 2002
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2002)0760314artptv2.0.co2
Subject(s) - photodynamic therapy , antagonist , chemistry , pharmacology , medicine , receptor , organic chemistry
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)‐4 H ‐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.