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.