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 porphyrins by cancer cells. Cancer cells also have elevated levels of mitochondrial benzodiazepine receptors which bind porphyrins with high affinity.


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 [3H] PK11195 binding to cancer cell homogenates and isolated kidney mitochondrial membranes.


RESULTS
We show that therapeutic potencies of porphyrins correlate closely with affinities for mitochondrial benzodiazepine receptors. Sensitivities of tumor cell lines to photodynamic therapy parallel their densities of these receptors.


CONCLUSIONS
We propose that porphyrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors.
Verma
A
A
Department of Neurology, Uniformed Service University of the Health Sciences, Bethesda, Maryland, USA.
Facchina
S L
SL
Hirsch
D J
DJ
Song
S Y
SY
Dillahey
L F
LF
Williams
J R
JR
Snyder
S H
SH
D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D010778:Photochemotherapy; D011166:Porphyrins / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D011166:Porphyrins; D011963:Receptors, GABA-A