Photodynamic tumor therapy: Mitochondrial benzodiazepine receptors as a therapeutic target

被引:93
作者
Verma, A
Facchina, SL
Hirsch, DJ
Song, SY
Dillahey, LF
Williams, JR
Snyder, SH
机构
[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA
[5] Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA
关键词
D O I
10.1007/BF03401728
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 [SH] 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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页码:40 / 45
页数:6
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