Apoptotic Response to Photodynamic Therapy versus the Bcl-2 Antagonist HA14-1¶
- 1 January 2002
- journal article
- Published by Wiley in Photochemistry and Photobiology
- Vol. 76 (3) , 314-9
- https://doi.org/10.1562/0031-8655(2002)076<0314:artptv>2.0.co;2
Abstract
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.Keywords
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