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Photodynamic Tumor Therapy: Mitochondrial Benzodiazepine Receptors as a Therapeutic Target

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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.

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Acknowledgments

This work was supported by USPHS grant DA-00266, Research Scientist Award DA-00074 to S.H.S., ES-07076 to J.R.W., and a grant of the W.M. Keck Foundation (S.H.S.). A.V. was supported by a grant from The Defense and Veterans Head Injury Program.

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Authors and Affiliations

  1. Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

    Ajay Verma & Stephen L. Facchina

  2. Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland, 21205, USA

    David J. Hirsch &  Solomon H. Snyder

  3. Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Solomon H. Snyder

  4. Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Solomon H. Snyder

  5. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Shi-Yu Song, Larry F. Dillahey & Jerry R. Williams

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  1. Ajay Verma
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Additional information

Communicated by S. H. Snyder.

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense.

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Verma, A., Facchina, S.L., Hirsch, D.J. et al. Photodynamic Tumor Therapy: Mitochondrial Benzodiazepine Receptors as a Therapeutic Target. Mol Med 4, 40–45 (1998). https://doi.org/10.1007/BF03401728

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