Promotion of PDT efficacy by a Bcl-2 antagonist.
Photodynamic therapy (PDT) directed against the endoplasmic reticulum (ER) is also known to target antiapoptotic Bcl-2 family proteins. This effect is associated with the initiation of both apoptosis, a cell death pathway, and autophagy, an organelle recycling system that can lead to survival or cell death. In this study, we examined the ability of the Bcl-2 antagonist HA14-1 to promote the photodynamic efficacy of PDT directed at the ER. At concentrations that independently caused only a small loss of viability, HA14-1 markedly enhanced the proapoptotic and phototoxic effects of ER photodamage. These results provide additional evidence that the antiapoptotic properties of Bcl-2 constitute an important determinant of photokilling, and demonstrate that synergistic effects can result when PDT is coupled with pharmacologic suppression of Bcl-2 function.
Kessel
David
D
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI, USA. dhkessel@med.wayne.edu
D000818:Animals; D017209:Apoptosis; D001578:Benzopyrans / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004357:Drug Synergism; D004721:Endoplasmic Reticulum / Q000187:drug effects*; D007939:Leukemia L1210 / Q000188:drug therapy*; D009570:Nitriles / Q000494:pharmacology*; D010778:Photochemotherapy / Q000379:methods*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects* / Q000528:radiation effects*; D016896:Treatment Outcome
D001578:Benzopyrans; D009570:Nitriles; D019253:Proto-Oncogene Proteins c-bcl-2; C456800:ethyl 2-amino-6-bromo-4-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate