PHOTODYNAMIC TUMOR-THERAPY - MITOCHONDRIAL BENZODIAZEPINE RECEPTORS AS A THERAPEUTIC TARGET

Background: Photodynamic therapy employs photosensitive agents such as porphyrins to treat a variety of tumors accessible to light-emitting probes. This approach capitalizes on the selective retention of porphy rins by cancer cells. Cancer cells also have elevated levels of mitoch ondrial benzodiazepine receptors which bind porphyrins with high affin ity. Methods: Cultured cancer cell lines were exposed to porphyrin and porphyrin-like compounds and then irradiated with light. Cytotoxicity of this treatment was measured via clonogenic assays. ?Mitochondrial benzodiazepine receptor pharmacology was studied using [SH] PK11195 bi nding to cancer cell homogenates and isolated kidney mitochondrial mem branes. Results: We show that therapeutic potencies of porphyrins corr elate closely with affinities for mitochondrial benzodiazepine recepto rs. Sensitivities of tumor cell lines to photodynamic therapy parallel their densities of these receptors. Conclusion: We propose that porph yrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors.