Photodynamic tumor therapy: Mitochondrial benzodiazepine receptors as a therapeutic target

Ajay Verma, Stephen L. Facchina, David J. Hirsch, Shi Yu Song, Larry F. Dillahey, Jerry R. Williams, Solomon H. Snyder

Research output: Contribution to journalArticle

Abstract

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. Conclusion: We propose that porphyrin photodynamic therapy is mediated by mitochondrial benzodiazepine receptors.

Original languageEnglish (US)
Pages (from-to)40-45
Number of pages6
JournalMolecular Medicine
Volume4
Issue number1
StatePublished - Apr 4 1998

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Verma, A., Facchina, S. L., Hirsch, D. J., Song, S. Y., Dillahey, L. F., Williams, J. R., & Snyder, S. H. (1998). Photodynamic tumor therapy: Mitochondrial benzodiazepine receptors as a therapeutic target. Molecular Medicine, 4(1), 40-45.